Cosmeticsandtoiletries201505 DL PDF

May 2015
Blurring Product
Categories p 2
Natural Preservatives to Maintain Microflora p 22
Sea Anemone Delivery of Collagen, γ-PGA p 54

Natural Retinol, Lipid Stabilizer p 64
Topical Skin Nutrition p 76
C&T Summit is getting closer! p 81
CT1505_Cover_1st.indd 1 4/10/15 5:01 PM

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Untitled-1 1 1/14/15 10:13 AM

Visit us at
NYSCC
Suppliers’ Day
May 12-13, 2015
Booth 531
Grant_Water.indd 1 4/7/15 2:53 PM

C&T May 2015 Editor’s note | C&T
Cover art by James Fergus
2 Editor’s Note
6 Scientific Advisors
88 Advertisers Index
Rachel L. Grabenhofer
Market Intelligence
8 Beauty Industry Growth: Mature Markets Offer blurring product categories
Safer Investments by R. Walker
It’s refreshing to emerge after a long, cold winter to greening
12 Finished Product Launches grass and budding trees—which means it’s time for spring clean-
14 Read the Label: Yes to Coconut, Head-to-Toe ing. I’ve become a fan of household cleansers that function across
Restoring Balm by S. Raffy mediums, i.e., from wood and glass, to metal. In many ways, these
are the “BB” and “CC” creams of the household world.
16 Technology Launches Technology transfer like this is not new but it has blurred
product categories, which is new. While this has created new
Regulatory categories, it has also negatively impacted others. Skin care and
18 Asia-Pacific Update on Korean Organic color cosmetics, for example, now include UV protection, which
Standards by K. Yarussi-King according to Euromonitor has hurt traditional sun care products.
It seems that companies can no longer just build on core skin,
Research hair or sun care categories; they must “cross-link” these areas to
provide unique synergies.
22 Natural vs. Synthetic Antimicrobials and The present collection of articles highlights technologies that
HDAC as an Indicator of Microflora Health cross and, in some cases, blur product categories. For example,
by M. Danaher, D. Schulz, E. Segura and natural antimicrobials are shown to preserve microflora. Topi-
M. Darley cal vitamin D and sea anemone “stinging” cells deliver wellness
36 Silica Nanoparticles for Increased Cosmetic and anti-aging benefits, respectively. Also, bakuchiol is a natural
Ingredient Efficacy by S. Nafisi, PhD, and ingredient that can stabilize retinol and lipids.
H.I. Maibach, MD Following this approach of building
on core strengths and cross-linking them,
online Problems with Skin Protectants Part 3, A New Cosmetics & Toiletries (C&T) announces
Shielding Concept by G. Pantini, PhD some exciting changes. First, I’d like
to introduce Kevin Campbell as our
Testing new managing editor for C&T. He will
46 Defining and Controlling Frizz strengthen our content for cosmetics R&D,
by T.A. Evans, PhD taking the brand to the next level. With
his addition, I will step into a new role as
54 Sea Anemone Delivery of Collagen and the Scientific Acquisitions Editor. While
γ-PGA for Anti-aging Benefits by Y. Tal, PhD, I’ll still be procuring technical content for
Kevin Campbell
E. Danon, A. Toren, PhD, and A. Khaiat, PhD C&T, I’ll also be doing it for our sister brands in the perfume,
online Biomimetic vs. Traditional Skin Moisturization: flavor, medical spa and related industries. In essence, I am “cross-
An In vivo Comparison by P. Todorova et al. linking” our company’s brands through science. You will continue
to see me at some industry conferences, but in a new and different
Formulating capacity. Please help me welcome Kevin-who, by the way, will be
at Suppliers’ Day so be sure to stop and introduce yourself.
64 Bakuchiol to Stabilize Retinol and
Polyunsaturated Lipids
by R.K. Chaudhuri, PhD, and B. Ou, PhD
76 Topical Delivery of Vitamin D for Well-Being
by C. Hilling
84 SPONSORED–Rosamox: Rosemary as Never To view the online articles listed:
Experienced Before by Kemin Personal Care
86 SPONSORED–Ethylhexylglycerin: Highly Pure
Quality by Patented Stabilization by schülke inc.
Pantini Todorova
2 | www.CosmeticsandToiletries.com Vol. 130, No. 4 | May 2015
CT1505_TOC_Ed_Note_fcx.indd 2 4/20/15 9:40 AM

Untitled-1 1 5/7/14 1:57 PM
Editorial
Director Jo-El M. Grossman
Managing Editor Kevin Campbell
1-630-344-6068/kcampbell@allured.com
Scientific Acquisitions Editor Rachel L. Grabenhofer
1-630-344-6072/rgrabenhofer@allured.com
Associate Editor Katie Anderson
1-630-344-6077/kanderson@allured.com
Advertising Sales
Vice President Brian O’Rourke
1-630-344-6030/borourke@allured.com
Business Development Manager
US (NJ & PA), Canada, Central &
South America/C&T Summit Tom Harris
Exhibits & Sponsorships 1-201-445-4702/tharris@allured.com
Business Development Manager
All US states except NJ & PA/ Kim Jednachowski
C&T Summit Exhibits & Sponsorships 1-630-344-6054/kjednachowski@allured.com
Business Development Manager Jane Evison
Europe & Asia 44(0)-1430-441685/jane-evison@btconnect.com
Business Development Manager Paige Crist
Fragrance 1-630-344-6060/pcrist@allured.com
Marketing Specialist Brittany Best
1-630-344-6076/bbest@allured.com
Coordinator Kasia Smialkowski
1-630-344-6025/ksmialkowski@allured.com
Audience Development
Director Linda Schmitt
Customer Service Jamie Schmidt
1-888-355-5962/customerservice@cosmeticsandtoiletries.com
DesigN
Manager Andrew Frederick
Graphic Designer James Fergus
Production Manager Bryan Crowe
Events
Group Show Director Sandy Chapin
Show Manager Mary Richter
1-630-344-6023/mrichter@allured.com
Corporate
President Janet Ludwig
Controller Linda Getner
Digital Products Director Rose Southard
Executive Assistant Maria Romero
Other products brought to you by Allured:

Alluredbooks, Cosmetics & Toiletries Bench Reference (CBR), Cosmetics & Toiletries magazine: Portuguese edition, Cosmetics
& Toiletries Summit, GCI (Global Cosmetic Industry) magazine, Perfumer & Flavorist magazine, Flavorcon, World Perfumery
Congress, Allured’s FFM Buyer’s Guide, Skin Inc. magazine, Face & Body Midwest Spa Conference & Expo, and Face & Body
Northern California Spa Conference & Expo
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CT1505_Masthead_fcx.indd 4 4/10/15 5:13 PM

CREATING TOMORROW’S SOLUTIONS
WHEN LOOK, FEEL AND PERFORMANCE

REALLY MAT TER ... IT’S SILICONES
FOR PERSONAL CARE.
NYSCC SUPPLIERS’ DAY

MAY 12-13, 2015
NJ CONVENTION & EXPO
CENTER, EDISON, NJ
Visit us at Booth 145
www.wacker.com/personal-care
WACKER is an innovative, global company specializing in a comprehensive silicone product

portfolio for applications in the personal care industry ranging from hair and skin care to
color cosmetics and sun care. We focus on advancing your current and future success with
our state-of-the-art BELSIL® silicones and HDK® fumed silica.
To help you differentiate your products and learn more about our solutions, visit us at
www.wacker.com/personal-care, or simply use your smartphone to scan the QR code.
Wacker Chemical Corporation, 3301 Sutton Road, Adrian, MI 49221, USA

TEL: +1 888 922 5374, FAX: +1 517 264 4068, info.usa@wacker.com
Untitled-1 1 4/9/15 9:43 AM

Scientific Advisory Board | C&T
“Today’s consumer is so busy, they want to cut the amount of time it takes to do any
function–their beauty routine included. With the introduction of alphabet creams
(BB, CC, etc.), multifunctional product launches have seen exponential growth. These
save consumers time without sacrificing quality and efficacy. Tremendous crossover is
seen between sun protection and higher broad-spectrum SPFs with anti-aging treatments;
sunscreen in color products; and anti-aging treatments in color products. Multifunction-
ality has even moved into the hair care arena and, more recently, supplements
(for skin care benefits). The multifunctional trend is continuing to grow and expand.”
Mindy Goldstein, PhD
Atlantic Coast Media Group
Eric Abrutyn Prithwiraj Maitra, Leslie C. Smith,

TPC2 Advisors Ltd. PhD PhD
Johnson & Johnson Coty-Lancaster
Zoe Diana Jennifer Marsh, David C. Steinberg

Draelos, MD PhD Steinberg & Associates
Dermatology Procter & Gamble
Consulting Services
Angela R. Eppler, Marc Pissavini, Peter Tsolis

PhD PhD The Estée Lauder
Pfizer Consumer Coty-Lancaster Companies
Healthcare
Trefor Evans, PhD Luigi Rigano, PhD Russel Walters,

TA Evans LLC Industrial Consulting PhD
Research Johnson &
Johnson
S. Peter Foltis, Sylvianne Xiao Wu, PhD

PhD Schnebert, MD Eli Lilly and Co.
L’Oréal LVMH Recherche
Shuzo Ishidate, Ron Sharpe Shuliang Zhang,

PhD Amway Corp. PhD
Shiseido Research Unilever
Center
CT1505_Adv_Brd_fcx.indd 6 4/10/15 5:17 PM

Untitled-1 1 3/27/15 12:00 PM
Market Intelligence | C&T
Beauty Industry Growth:

Mature Markets Offer
Safer Investments
Robert Walker, Euromonitor International
T
he good news is that emerging market
consumers are still spending plenty of
cash on beauty and personal care. Value Growth in Beauty
sales across emerging markets were up almost
10% in 2014 over the previous year at fixed
U.S. dollar prices, according to new data from
Euromonitor International.
The bad news is that annual growth
failed to reach double-digit levels for the first
time in more than a decade. This may be
the start of an era of more subdued emerg-
ing market demand–and subdued future
growth makes sense. Emerging markets’ sales
performance has been in a state of flux over
2013–2014, as global beauty and personal
care brands battle with a more reticent China,
a more cash-strapped Brazil and a more
inward-looking Russia.
n Value sales across emerging markets were up almost
However, the situation is set to worsen.
10% in 2014 over the previous year.
Latin America is teetering on the edge of
recession, Eastern Europe is in conflict, the
n Developed markets and the United States could soon be
Middle East and Africa are in varying degrees
outperforming emerging markets in key industry categories.
of upheaval, and emerging Asia is losing its
economic dynamism. In addition, currency
n Some of the beauty industry’s strongest performing
instability in key countries, such as Brazil, imports in China over 2013–2014 came from South Korea.
Mexico, Turkey and South Africa, is creating
havoc in terms of strategic planning.
n Brazil’s beauty and personal care retail sales grew 11% in
These factors will conspire to turn former 2014 over the previous year at fixed U.S. dollar prices.
safe havens of growth into hotbeds of uncer-
tainty. It is true that emerging market growth
n India was one of the best performing emerging markets
in 2014 was still much stronger than the for beauty and personal care in 2014, with retail sales
Save to
My Library 2% growth in developed markets. However, climbing 15% from 2013.
developed markets are starting to look like a
Reproduction in English or any other language of

8 | www.CosmeticsandToiletries.com all or part of this article is strictly prohibited. Vol. 130, No. 4 | May 2015
© 2015 Allured Business Media.
CT1505_Mrkt_Rprt_fcx.indd 8 4/10/15 5:25 PM

Untitled-1 1 4/1/15 11:38 AM
safer investment target than emerging markets over However, growth was slower in comparison with
the next five years. the preceding two years, with 14% and 16% growth
Indeed, in a pendulum swing that few in the in 2013 and 2012, respectively. It is also hard to see
industry saw coming, developed markets and the how growth will avoid a further drop in 2015, as the
United States in particular could soon be outper- Brazilian economy reaches the brink of recession.
forming emerging markets in key industry categories. One of the problems for the beauty industry is
that mid-income Brazilians have grown used to pres-
Single-digit Growth is the tigious possessions, such as smart phones, satellite
New Norm in China TVs and cars. As spending power weakens, these are
China has been a magnet for beauty industry the types of products and services most households
investment over the last decade, spurred on by the will want to retain for as long as possible.
country’s rapid economic growth. However, Western Inevitably, that means savings will have to be
companies with significant Chinese exposure, such made in other areas. Will beauty and personal care
as Procter & Gamble, L’Oréal and Unilever, are not be among the casualties? They might be. At the very
sitting as pretty as they were three years ago. least, there is likely to be much stronger trading down
by consumers in product categories including hair
care, deodorants and men’s grooming.
As spending power India Could be the New China
weakens in Brazil, will India was one of the best performing emerging
markets for beauty and personal care in 2014, with
beauty and personal retail sales climbing 15% from 2013. Among the
major emerging markets, India also has some of the
care be casualties? best growth prospects over the next five years.
As a major oil importer, India’s economy is
They might be. notably being boosted by cheaper oil prices. This
will filter though into the pockets of increasingly
beauty-conscious urban consumers. These trends
Sales are still growing, reaching $48 billion in thus bode well for fast-growing beauty and personal
2014, with growth of 7% from 2013. However, this care categories, such as deodorants, color cosmetics
was the third consecutive year of slower growth, and men’s grooming.
according to Euromonitor International. This is
not only due to economic issues. China’s economy
A Pendulum Shift in the
is slowing, but the consumption culture of China’s Making
mid-income consumers also is changing. The urban Over the last decade, the beauty industry relied
mid-income group is now more discerning and, to heavily on emerging markets to shore up worldwide
an extent, wary of Western brands. This wariness is growth. This trend continued in 2014, but the once
rooted in a government crackdown on extravagance. cavernous gap in growth between emerging and
There is also a growing undercurrent of per- developed markets could now start to narrow, fueled
ception that Western brands do not always match by resurgent consumer confidence in the United
Chinese tastes and requirements. It is telling, perhaps, States and some Western European countries.
that some of the beauty industry’s strongest perform- Growth in emerging markets has not run its course.
ing imports in China from 2013-2014 came not from However, a long period of double-digit U.S.-dollar
France or the United States, but from South Korea. growth has finally fizzled out, and moderate growth
This reflects a strong Chinese affinity with South is set to be the new norm in key countries such as
Korean soap operas and popular music. China and Brazil.
As a result, strategic planning for leading global
Consumers Trade Down in players is likely to a see major revision over the next
Brazil as Economy Implodes three years, with a stronger investment focus on
Brazil’s beauty industry grew even faster than developed countries. For brands that get the mix
China’s over the last decade in absolute terms. It con- right, the global impact should not be too bad.
tinues to flout strong external signs of growth, with Editor’s note: To read this full market report, see the May issue
beauty and personal care retail sales growing 11% in of GCI magazine or visit www.GCImagazine.com.
2014 over the previous year at fixed U.S. dollar prices.
CT1505_Mrkt_Rprt_fcx.indd 10 4/10/15 5:25 PM

Untitled-3 1 4/7/15 3:46 PM
Finished Product Launches

Cactus Moisture retention
G.M. Collin | www.gmcollin.com
G.M. Collin designed a new treatment to moisturize and soothe dry, irritated skin and improve its barrier function.
Nutriderm Replenishing Complex contains Barbary cactus seed oil to help the skin retain moisture while protecting
against free radicals. The oil also promotes new cell growth and calms inflammation. Argan oil is included to
moisturize and prevent transepidermal water loss. Omegas 3, 6 and 9 soothe and moisturize skin while vitamin E
conditions and provides antioxidant protection. By improving barrier properties, the complex improves elasticity
and increases hydration while protecting the skin from transepidermal water loss. The product is recommended for
normal to dry skin types and is suitable for sensitive skin.
Ingredients: Caprylic/Capric Triglyceride, Argania Spinosa Kernel Oil, Simmondsia Chinensis (Jojoba) Seed Oil,
Isostearyl Avocadate, Tocopheryl Linoleate (Vitamin E), Pollen Extract, Glycine Soja (Soybean) Oil Unsaponifiables,
Olea Europaea (Olive) Oil Unsaponifiables, Triticum Vulgare (Wheat) Germ Oil Unsaponifiables, Lupinus Albus
Seed Oil, Opuntia Ficus Indica Seed Oil, Prunus Armeniaca (Apricot) Kernel Oil, Solanum Lycopersicum (Tomato) Extract,
Phytosteryl/Octyldodecyl/Lauroyl Glutamate, Lavandula Stoechas Extract, Tocopherol (Vitamin E), Fragrance (parfum),
Helianthus Annuus (Sunflower) Seed Oil, Rosmarinus Officinalis (Rosemary) Leaf Extract.
Coconut Milk Moisture

Kiss My Face | www.kissmyface.com
Kiss My Face focused on the hydrating benefits of coconut milk for its new soap launch. Pure Coconut Milk Bar
Soaps are formulated with 86% pure coconut milk and oil, which are known for their moisturizing properties.
The soap is available as Pure Coconut Milk Soap or with lime peel, to add natural exfoliation.
Ingredients: Pure Coconut Milk Soap with Lime Peel: Sodium Cocoate (Coconut) Water, Sodium Olivate
(Olive) Oil, Glycerin (from Coconut), Natural Fragrance, Cocos Nucifera (Coconut) Oil; Cocos Nucifera
(Coconut) Milk; Citrus Aurantifolium (Lime) Peel; Sodium Chloride (Sea Salt).
Coconut for Curls

Pureology | www.pureology.com
Pureology created its first line of hair care products devoted to treating stressed, color-treated waves and curls. Curl
Complete contains coconut oil and the company’s AntiFade Complex to revive hair’s original curves while helping to
control frizz, reduce breakage and enhance shine for 72 hours. The system includes a shampoo, conditioner, taming
butter, mask, styling spray gel and primer/refresher. Cold-pressed coconut oil is included for its high vitamin E
and fatty acid content to condition and hydrate. It was found to soothe scalp dryness, prevent dandruff and keep
hair from drying out. The company’s complex is a combination of Sederma’s Heliogenol and vitamins C and E to
neutralize free radical damage and maximize color retention. The Moisture Melt Masque provides deep conditioning
to enhance curl definition and add bounce.
Ingredients: Moisture Melt Masque: Water (aqua), Hydroxypropyl Starch Phosphate, Quaternium-87, Stearyl Alcohol,
Behentrimonium Chloride, Stearamidopropyl Dimethylamine, Cocos Nucifera (Coconut) Oil, Propylene Glycol, Phenoxyethanol,
Caprylyl Glycol, Amodimethicone, Fragrance (parfum), Candelilla Cera (Candelilla) Wax, Isopropyl Alcohol, C11-15 Pareth-7,
Citric Acid, Benzoic Acid, Laureth-9, Glycerin, Tocopherol, Benzophenone-4, Trideceth-12, Benzyl Alcohol, Linalool, Benzyl
Salicylate, Limonene, Geraniol, Helianthus Annuus (Sunflower) Seed Extract, CI 15985 (Yellow 6), Melanin.
Suppliers Referenced
Heliogenol (INCI: Butylene Glycol (and) Helianthus Annuus (Sunflower) Seed Extract) is manufactured by Sederma, www.sederma.fr.
Ingredients/claims are published as provided to C&T magazine by the manufacturers.
CT1505_FP_Launches_fcx.indd 12 4/20/15 9:53 AM

Come to
NYSCC Suppliers’ Day 2015
Visit INNOSPEC Booth 1431

May 12-13, Edison, NJ
innerr beauty
b
INNOSPEC knows that beauty is
more than skin deep. That’s why
everything that goes into our
personal care products is inspired,
evaluated, and perfected before
earning the right to touch the
lives of the people who rely on us.
INNOSPEC can help find the

products that will work beautifully
for you.
Visit innospecinc.com/personalcare
Untitled-1 1 4/3/15 3:44 PM

Honey skin Treatment

Read the Label Manuka Health | www.manukahealth.co.nz
New Zealand-based Manuka Health introduced

to the U.S. market a duo of targeted skin
Yes To Coconut Head-to-Toe treatments for troubled skin that center around
Restoring Balm the company’s star ingredient—manuka
honey. This honey is manufactured by bees
“It’s the balm!” Yes To claims that pollinate the country’s native Manuka
its Yes To Coconut Head-to- bush (Leptospermum scoparium), which has
Toe Restoring Balm is a “super antibacterial, antifungal and antioxidant
moisturizing balm, clinically properties. The honey is said to assist in
proven to moisturize dry, cracked wound-healing, nourish the skin, support cell growth
and fight the visible signs of aging. The products in the
skin.” This “98% natural” product
ManukaClear line, which includes a mask and intensive
is said to be the perfect remedy
BB gel, are formulated with two of the company’s
for dry elbows, hands, knees or
ingredients: MGO 600+ Manuka Honey and MGO 400+
toes. This column will review the
Manuka Honey with CycloPower. Each honey contains
ingredient listing for functionality
a specified amount of methylglyoxal (MGO), which is
and claims substantiation. responsible for the bioactive properties of the ingredient.
The formula is an anhydrous balm with coconut, sweet almond, CycloPower is a cyclodextrin designed to boost the
sunflower and avocado oils as the primary vehicle/diluent. Shea bioactivity of the honey in the human body. In addition
and cocoa seed butter provide additional emollience to help protect to these ingredients, the BB gel contains manuka essential
skin from dehydration and restore skin’s suppleness. Beeswax and oil and aloe vera gel to smooth skin texture and maintain
silicone dioxide thicken and stabilize the oils to form the solid balm. healthier-looking skin.
The “bio-active” or cosmeceutical ingredients include phytosteryl
canola glycerides and extracts of Aleurites moluccana (kukui) seed, Ingredients: Intensive BB Gel: Leptospermum Scoparium
Hibiscus sabdariffa (roselle) flower, Morinda citrifolia (noni) fruit, Mel (MGO 600+ Manuka Honey), CycloPower with
Musa sapientum (banana) fruit, Orchis mascula (purple orchid) flower MGO 400+ Manuka Honey, Leptospermum Scoparium
and Psidium guajava (yellow guava) fruit. Mixed tocopherols are in a (Manuka) Oil, Aloe Barbadensis (Aloe Vera) Powder.
soybean oil carrier and provide antioxidant protection for the oils and
butters in the formula. There is no preservative in the formula, since it
is not required for an anhydrous formula. Women’s Hair Growth
Rogaine | www.rogaine.com
Johnson & Johnson added a 5%

minoxidil treatment to its Rogaine
line for women who face thinning
hair or hereditary hair loss. Women’s
Rogaine 5% Minoxidil Topical
Aerosol is the first and only U.S.
Food and Drug Administration
Fragrance is high in the ingredient deck, and ingredients (FDA)-approved, once-daily use
listed after it are most likely at 1% or less. The formula is indeed treatment for female pattern hair
“petroleum-, SLS- and paraben-free,” and the product’s ingredients loss. This foam formula delivers the active to the scalp,
do support the marketing claims. I am not sure why citric acid is where it penetrates to re-activate hair follicles and
stimulate hair regrowth. The formulation also features
included in the formula unless it is present in one of the individual
an enhanced biodelivery system that breaks down with
raw materials.
body heat to deposit actives on the scalp without leaving a
Susan Raffy, Susan Raffy Consulting residue, making styling easier.
Active Ingredients: Minoxidil 5% w/w (without

The viewpoints expressed in this column are those of the author and propellant) Inactive Ingredients: Butane, Butylated
do not necessarily reflect those of Cosmetics & Toiletries.
Hydroxytoluene, Cetyl Alcohol, Citric Acid, Glycerin,
Isobutane, Lactic Acid, Polysorbate 60, Propane, Water
(aqua), SD Alcohol 40-B, Stearyl Alcohol.
CT1505_FP_Launches_fcx.indd 14 4/14/15 1:56 PM

Polyethylene-Free Scrubbing
Bead Stability Results
Don’t Risk Formula Instability
Floratech has made stable,

biodegradable, exfoliating
beads since the 1980s.
Floratech evaluated many
Stable Unstable competing polyethylene-
free scrubbing beads
Comprehensive Bead Stability Study Results in multiple surfactant
systems.
Available upon request
To request a free copy of
INCI Name:
Exfoliating Wash Test Solution #3 at 43°C this comprehensive report
please scan the QR code.
.
www.floratech.com
Stability in weeks: 0 1 2 3 4 5 6 7 8 9 10 11 12 sales@floratech.com
1.480.545.7000
For a copy of this free, comprehensive particle stability analysis please contact sales@floratech.com
Suppliers’ Day Stand 1446
Untitled-1 1 4/13/15 10:12 AM

Technology Launches
NEW FROM
Reducing Skin oils Shea Moisturization

Silab’s new dog rose extract, Clear, transparent
Sebocytine (INCI: Rosa Canina oils are trending
Fruit Extract), is a sebum-regulating in the United
ingredient rich in wild rose berry States and Europe,
flavonoids that improves the and in relation,
comfort of Caucasian and Asian AAK Personal
skin. In 2D and 3D models of Care has created
human sebocytes, the extract a clear liquid shea
limited sebocyte differentiation oil to soften and
and lipogenesis, in turn reducing moisturize the skin and hair. The physical and sensory
sebum secretion and the surface attributes of Lipex SheaClear (INCI: Butyrospermum
of pores. These actions limit shine and skin imperfections. In Parkii (Shea) Oil) make it ideal for oils where clarity or low
male and female volunteers, it also was found to normalize sebum color is desired. The product contains high levels (6-8%) of
production, tighten pores and control shine. Thus, skin is purified functional unsaponifiables, which help to revitalize skin and
and freed from imperfections, restoring both comfort and beauty. restore shine and softness to hair. The ingredient exhibits
The extract is recommended in all mattifying and anti-blemish no adverse crystallization effects or settling over time, and it
skin care to improve comfort for combination to oily skin types. It can be used in high-end cosmetic formulations as the main
is compliant with European, U.S., Japanese and Chinese cosmetic emollient or in combination with other oils and esters to
regulations. customize sensory properties. Due to a low melting point, it
www.silab.fr is also suitable for cold-processed emulsions.
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Quillaja Cleansing Lifting Active

Naturex sourced quillaja to Sederma debuted its
create a natural surfactant. lifting active for the face
Since it is rich in saponins, and neck. Majestem
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Saponaria Wood Extract Alpinum Callus Culture
(and) Sodium Benzoate) Extract (and) Glycerin
possesses unique foaming (and) Xanthan Gum)
properties. The Andean helps recreate dermal
people have used quillaia matrix tension through
to clean skin and treat mitochondrial dynamism
skin disorders for centuries, and research has confirmed its repair and extracellular
calming and dermo-purifying properties. Sustainably sourced matrix maintenance. This plant cell culture neutralizes the
in the Chilean forest, the plant is efficiently processed in a oxidative stress caused by pollution and irradiation to lift
facility located close to harvesting areas. This quillaja extract the skin. In three weeks, sagging neck skin was found to
can be used as a natural non-ionic surfactant. It is also non- tighten from 10.6% to 56%, and neck folds were evened
allergenic, bringing softness and naturalness to skin, hair, out. After six weeks, cheeks also were visibly lifted, and
baby and oral care products. crow’s feet were smoothed from 11% to 75%. This active
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www.sederma.fr
CT1505_Tech_Launches_fcx.indd 16 4/13/15 10:59 AM

NEW FROM
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subsidiary of SEPPIC,
with excellent foam and
launched its first
pleasing rheological
macroalgal cell culture
properties, Evonik launched
innovation. Ephemer
a concentrated surfactant
(INCI: Not Provided) is
based on Roundtable on
a gametophyte extract
Sustainable Palm Oil (RSPO)
taken from macroalgae
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cells grown in a laboratory and harvested at an ephemeral
TEGO Betain P 50 C (INCI:
stage in the life cycle of Undaria Pinnatifida seaweed. During
Cocamidopropyl Betaine) lends an improved cost/performance
this growth stage, cells accumulate antioxidant molecules. The
ratio compared with standard CAPBs. This 38% active betaine
resulting extract protects the skin within 24 hours by acting
provides thickening performance, is easy to process, and delivers
on the mitochondria and quickly reducing free radicals. After
generous foam combined with a pleasant skin feel. The palm-
eight days, it preserves mitochondrial DNA, which is essential
based feedstock is predominantly renewable and, coupled with
for proper cell functioning. After 28 days, the skin is better able
the high purity of its preservative-free betaine, supports an
to fight free radicals that cause skin aging. Finally, after 56 days,
environmentally conscious formulating approach. The ingredient
the skin’s micro-relief is markedly improved, as compared with
is suitable for a range of applications, including body washes,
a placebo.
shampoos, liquid soaps, foam baths, oral care and soap bars.
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Washing with oils Intense Moisturization

Croda developed an effective TRI-K provides immediate
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East, Cithrol 10GTIS (INCI: to its moisturizing
Not Provided) enables the properties, Fision
incorporation of oils into Hydrate (Water (aqua)
cleansers to gently and (and) Sodium PCA (and)
efficiently cleanse and soften Wheat Amino Acids (and)
the skin while also easily Panthenol (and) Glycerin
rinsing away with water. (and) Sodium Hyaluronate
The ingredient can be used (and) Hydroxyproline) was shown to reduce transepidermal
to formulate clear o/w microemulsion facial cleansers, water loss, compared with a placebo, and therefore increase
maintaining the perfect hydrophilic-lipophilic balance skin barrier function. Based on a consumer perception
required for this type of high performance system. study, the moisturizer instantly left skin feeling smoother
www.croda.com and better moisturized, compared with a commercial lotion
and the placebo. Consumers also felt it improved absorbance
while limiting perceptions of tackiness and greasiness. The
ingredient is designed to improve hydration, support barrier
function, and quench the skin’s thirst.
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Vol. 130, No. 4 | May 2015 Cosmetics & Toiletries® | 17
CT1505_Tech_Launches_fcx.indd 17 4/13/15 11:00 AM

Regulatory | C&T
Asia-Pacific Update on
Korean Organic Standards
Karen Yarussi-King
Raleigh, N.C., USA
O
n Dec. 24, 2014, the Korean Ministry of Food and Drug Safety
KEY WORDS (MFDS) passed Regulation 2014-20, the Regulation on Organic
Cosmetics Standards,1 which will go into effect on June 24, 2015. On
Korea • organic • plants • its website, the MFDS stated this regulation was passed to: prevent the flood
animal-derived ingredients • of incorrect organic products into Korea, provide consumer education,
minerals • processing • create criteria for organic products, and ensure a quality supply of organic
manufacturing products into Korea.
This regulation recognizes four categories of organic ingredients and
two categories of approved processing methods. In addition, it defines other
approved and unapproved elements of organic products, which are defined
ABSTRACT and outlined herein.
The new Korean
Regulation on Organic Four Pillars of Organic Ingredients
The four categories of organic ingredients outlined by the MFDS
Cosmetics Standards,
include: plant, animal-derived, mineral and certified organic ingredients.
which goes into effect on
Plant ingredients: This category includes unprocessed plant ingredients
June 24, 2015, has set including those of marine (algae) origin, in addition to those processed
forth guidelines for raw using an approved physical or chemical/biological method.
material sourcing and Animal-derived ingredients: Similar to plant ingredients, this category
processing of organic includes unprocessed animal ingredients such as eggs, milk and milk
cosmetic products, proteins, as well as animal by-products made using an approved physical or
as outlined here. This chemical/biological processing method. Cells, tissues and organs of animals
regulation aims to prevent are excluded from this category.
Mineral ingredients: Minerals formed naturally by geological processes
incorrect organic products
or processed using approved physical methods are included in this category,
and ensure a quality as well as 84 accepted mineral-derived ingredients processed using a chemi-
supply of organic products cal/biological method. These 84 minerals can be found in Appendix I of the
by establishing criteria for regulation; they include many mineral-derived colorants. Fossil fuels are
their creation. excluded from this category.
Certified organic ingredients: This category includes organic agricul-
tural fishery goods processed using an approved physical method and/
or certified organic by a body that follows government standards. Also
Save to
included are ingredients certified organic by bodies registered with the
My Library
International Federation of Organic Agricultural Movements (IFOAM), and
processed using an approved physical method.

CT1505_Regulatory_Yarussi_irv.indd 18 4/13/15 11:09 AM

Untitled-1 1 1/20/15 11:27 AM
Regulatory | C&T
Organic Cosmetic Standards In addition to these requirements for organic
In addition to the organic ingredients outlined, products in Korea, manufacturers will have added
an organic product may contain water; but at least record-keeping requirements: all substantiation
10% of the product must be organic ingredients. documents for products must be maintained for
This 10% organic content is calculated based on the either three years or one year after the expiration
weight ratio. In other words, if an extract mixture is date/imported date, whichever is longer.
used at 1% but is made up of 25% organic extract plus Lastly, two key manufacturing practices must be
74% water plus 1% of an approved preservative, only followed for organic products. First, facilities must
0.25% can be counted toward the organic content. be sanitized using only the approved sanitizers listed
In principle, synthetic ingredients cannot be in Appendix 5, to prevent cross-contamination. Also,
used unless they have no natural substitute. These organic and other ingredients must be clearly labeled
synthetics include: natural tocopherol extracted using for identification, and may not be stored in polyvinyl
hexane; denatonium benzoate; dehydroacetic acid chloride or polystyrene foam containers.
salts; lecithin; benzoic acid salts and esters; benzyl
alcohol; salicylic and sorbic acid salts; alkyl betaine; References
isopropyl alcohol; xanthan gum; carrageenan; 1. www.mfds.go.kr/eng/index.do (Accessed Mar 23, 2015)
tetrasodium glutamate diacetate; and tertiary butyl

alcohol (TBA).
Furthermore, as noted in Appendix 4, the Contributing author
ingredients used in organic products may not contain
specific contaminants, including trace heavy met-
Karen L. Yarussi-King is a
als, hydrocarbons, agricultural pesticides, dioxins,
regulatory expert with more
radioactive materials, genetically modified organ- than 25 years of experience
isms and by-products, residual animal medicines managing regulatory affairs for
(steroids), plant pollutants (nitrates), mycotoxins the industry’s major brands. After
and nitrosamines. obtaining her bachelor’s degree
in political science in 1988 from
Processing and Manufacturing Albertus Magnus College, Yarussi worked for
Various physical, chemical and biological process- the U.S. Department of Commerce and National
ing methods are permitted, as listed in Appendix 3 of Environmental Technology Applications Corp.
the regulation. Most are mechanical, involving steam She joined Schenectady International in 1993,
or natural solvents such as water, carbon dioxide and where she navigated chemical regulation in
different roles. In 1998 she joined Avon, initially
glycerin. Example physical processes are distillation,
as a regulatory affairs associate, then a senior
extraction, maceration, infusion and degumming/
associate, and eventually as program leader of
de-oiling. Approved chemical/biological methods are regulatory affairs. She went on to serve regulatory
alkylation, esterification, fermentation and hydro- management roles for Honeywell, Limited
genation. Forbidden processing methods include Brands Inc., Burt’s Bees Inc. and StriVectin before
bleaching/deodorization; irradiation; sulfonation; the starting her own regulatory consultancy, Global
use of ethylene, propylene or other alkylene oxides; Regulatory Associates Inc., in October 2013.
and the use of mercury and formaldehyde.
CT1505_Regulatory_Yarussi_irv.indd 20 4/13/15 11:09 AM

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Untitled-1 1 4/3/15 3:56 PM

Research | C&T
Natural vs. Synthetic Antimicrobials and

HDAC as an Indicator
of Microflora Health
Maureen Danaher, Durant Scholz,
Erica Segura and Meghan Darley
Active Micro Technologies, LLC, Lincolntown, NC USA
I
t is not surprising that skin, being the body’s largest organ and having
KEY WORDS constant exposure to the environment, is an ideal location for bacteria
growth. Such growth includes resident and transient pathogenic bac-
microflora • triclosan • teria, which are capable of invading the host and causing harm, as well
antimicrobial peptides • as commensal bacteria, which help to protect the host from pathogens.
histone deacetylase The skin provides a first line of defense against pathogens based on its
(HDAC) mechanical rigidity and low moisture content, production of lysozyme,
acidic environment, host defense peptides such as defensins, and as noted,
protective commensal microbes.1 Yet, some organisms can and do evade
ABSTRACT cutaneous host defenses, leading to the next line of protection, which
involves the immune system. This leads to the need for preservation and
This article reviews the antimicrobial efficacy, with the ultimate goal of ensuring product stability
role of skin microflora and consumer protection.
in protecting skin, and In the past, cosmetic formulators used preservatives and biocides for the
assesses how the histone sole purpose of inhibiting microbes. The Personal Care Products Council,
deacetylase (HDAC) for example, defined a preservative system as any agent added to a product
enzyme is implicated. to reduce or prevent microbial growth.2 Antimicrobial protection can be
achieved by preserving the products applied to skin, and/or by eliminating
From this, HDAC
harmful microorganisms that already inhabit the skin. However, it is essen-
expression is used as tial to bear in mind the skin’s protective microbiome because the choice of
an indicator to compare preservative could unintentionally alter the skin’s natural defenses.
the effects of traditional Take traditional biocides such as triclosan, for example, which are used
biocides and preservatives in hand sanitizers to disrupt bacterial cell walls. While providing broad-
with natural antimicrobials spectrum bactericidal action, they also have nonspecific targets and disturb
on skin’s microbiome. the skin’s microflora balance, killing both pathogenic and commensal
Results suggest the bacteria and leaving the skin defenseless against new destructive microor-
ganisms.3 Triclosan also can cause dangerous antimicrobial resistance to
latter effectively preserve
medicines,4 which is a growing threat to health care as a whole. In addition,
products while maintaining traditional preservatives such as parabens and formaldehyde donors histori-
a healthy microbiome. cally work well at inhibiting microbial growth, but it is not currently known
whether they affect or alter the body’s protective microbiota.3
While safety studies and cosmetic research over the past decade have
Save to generally succeeded in analyzing the potential toxicity of preservatives and
My Library
biocides to consumers before they reach the market, only more recently
have the effects of those products on skin’s protective commensal micro-

CT1505_Research_Danaher_fcx.indd 22 4/13/15 11:42 AM

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Untitled-1 1 4/1/15 11:36 AM

Research | C&T
biota been investigated. In relation, some natural hosts 10 times more microbial cells than human
preservatives have been found effective for killing cells,6 which reside in a symbiotic relationship
pathogenic bacteria while maintaining commensal between resident, transient and commensal bacteria.
microflora on the skin; these are described later. This ecosystem harbors a diverse range of microbial
Such elimination of “bad” bacteria and promotion communities that live on physiologically and topo-
of “good” bacteria is the ideal balance. This article graphically distinct areas, such as underarms, hands,
reviews the role of skin microflora in protecting skin, and feet, as a National Institutes of Health (NIH)
and assesses how the histone deacetylase (HDAC) microbiome study describes.7
enzyme is implicated. From this, HDAC expression For example, as shown in Figure 1, the primary
is used as an indicator to compare the effects of bacteria located on the human hands include Proteo-
traditional biocides and preservatives with natural bacteria and Bacteroidetes, both of which are major
antimicrobials on skin’s microbiome. phylum of Gram-negative bacteria.8 To contrast this,
some of the principal microbes located on the feet
Understanding include Staphylococcaceae and Corynebacterineae;
Commensal Microflora both are very different organisms from those found
Cosmetics and personal care products can sup- on different human body sites.
port the growth of Gram-negative and Gram-positive The NIH microbiome study analyzed ribosomal
bacteria, along with yeasts and mold, but some of RNA gene sequences obtained from twenty distinct
these also have nonpathogenic forms that reside as skin sites of healthy humans, and found that physi-
commensal microflora on the skin.5 So the question ologically comparable sites harbored similar bacterial
is, how do antimicrobial agents differentiate between communities. These results support the fact that the
protective and pathogenic microflora, to help main- complexity and stability of a microbial community is
tain the proper balance? dependent on the specific characteristics of the skin
To discuss the safety and effect of biocides and site and extrinsic environmental factors with which it
preservatives, it is essential to understand the natural comes into contact.7
skin microbiome. The diversity of the microbiome Some bacteria involved in the microbiome can
begins shortly after birth with the first microbial cause malady; these include resident and transient
colonization. With age, the average adult eventually bacteria, which are capable of invading the protective
Figure 1. Depiction of the human body and bacteria that predominate;8 Image courtesy of
www.genome.gov

Untitled-2 1 4/20/15 2:22 PM
Research | C&T
communities that defend against pathogens. On the which plays a crucial part in many physiological
other hand, protective or commensal bacteria use pathways such as skin inflammation.
competitive inhibition or excretory factors to protect HDAC can be responsive to many different envi-
the body from such pathogens. The same NIH study7 ronmental signals and therefore serves as an innovative
not only investigated these differences, but also marker for microflora balance. This is because when
examined the entire aspect of bacterial symbiosis to the enzyme functions properly, the microbial popula-
explore the microbial interdependencies and cross- tion of healthy skin remains intact, thus preserving
talk required to maintain healthy skin. skin’s integrity and natural barrier function. For exam-
Recent research has begun to document how ple, HDAC3, one of the most prominently expressed
such skin commensals interact with one another, histone deacetylases in N-TERT human keratinocyte
pathogenic microbes and human cells. Staphylococcus cells, has been shown to have many inflammatory and
epidermidis provides a classic example. This commen- metabolic roles related to the integrity and function of
sal Gram-positive bacterium secretes antimicrobial human organs such as the skin and intestines.12 Once
substances that help fight pathogenic invaders. A dif- the effects of HDAC on such downstream pathways is
ferent Gram-positive bacterium, Propionibacterium better understood, researchers could help consumers to
acnes, uses the skin’s lipids to produce short-chain better maintain their skin health by the routine applica-
fatty acids that can also ward off microbial threats.9 tion of products containing antimicrobials.
Yasmine Belkaid, of the National Institute of
Allergy and Infectious Disease, described the impor- HDAC and Inflammation
tance of this bacterial cross-talk precisely. “I think Three publications describing the supporting role
anything we can do to restore more balance or more HDAC plays in inflammation are of particular inter-
appropriate microbe composition in the skin, as in all est to the current discussion. First, a study13 from
the different tissues, is extremely important.”10 These the journal Nature found that HDAC3, while in the
and other skin microbes have an impact on the local presence of commensal bacteria, is a key mediator
molecular environment, and may, as a result, be able in maintaining the overall integrity and function of
to directly alter the behavior of human immune cells. human organs such as the intestines and skin. Major
differences were found between the microbial popula-
Histone Deacetylase tions in normal mice, compared with those deficient in
An example of how microbes may impact the the HDAC3 enzyme. When this enzyme was reduced,
local molecular environment of skin is provided by some bacterial species became over-populated, a loss
a class of enzymes known as histone deacetylases in barrier function was observed, and skin damage and
(HDACs). These enzymes help maintain healthy inflammation occurred. In addition, losses of the prin-
skin by balancing the acetylation activities of histone ciple cell type found in epithelium of small intestines
acetyltransferases on chromatin remodeling, and also were noted.
playing essential roles in regulating gene transcrip- These results indicate that HDAC plays a key role
tion.11 Gene transcription leads to protein expression, in the relationship between microbiota and inflam-

mation,13 and that fundamental changes occur in this relationship following the
deletion of HDAC3. These changes not only influence the microbiota, but also
cell behavior, including downstream gene expression. Without HDAC, a severe
loss of barrier function in the large intestine and reduction in colon length also
were observed;13 although this experiment focused on internal organs, it is con-
nected with skin care since epithelial barrier functioning applies to both. Further,
HDAC is present not only in internal organs but previous research has shown it is
expressed in epidermal keratinocyte skin cells (HaCaT).12
A second study,12 from the Journal of Cell Science, investigated HDAC protein
levels and total activity dependence on Aryl Hydrocarbon Receptor Nuclear
Translocator (ARNT) in N-TERT epidermal keratinocyte cells. Here, the
researchers employed an HDAC assay to quantify their findings. In relation, one
When HDAC3 enzyme was

reduced, some bacteria became
over-populated and a loss in
barrier function was observed.
laba utilized the same methods and assay to compare the microflora integrity of
keratinocytes treated with natural vs. synthetic preservatives. This work sought
to ascertain whether the expression of HDAC in the epidermis is critical to the
maintenance of skin health, keratinocyte differentiation and proper barrier func-
tion formation. The study found that ARNT-dependent shifts in HDAC activity
could be attributed to significant changes in levels of HDAC proteins present.
For example, depletion of ARNT led to an increase in HDAC protein levels and
activity, while over-expression of ARNT led to a decrease in HDAC activity.
ARNT is important because it controls both amphiregulin (AREG), the most
highly expressed epidermal growth factor receptor (EGFR) ligand in human
keratinocytes, and downstream inflammatory pathways, at least in part, by
modulating HDAC activity.12 All of these inflammatory and regulatory pathways
target advanced stages of epidermal differentiation, and may serve important
roles in skin pathologies such as psoriasis and atopic dermatitis. For instance, if a
certain biological or chemical stressor is introduced, a change in barrier function
is caused by altered immune responses via action on the cytosolic transcription
factor aryl hydrocarbon receptor (AhR) and ARNT. The decrease in ARNT then
leads to a downstream increase in HDAC level and activity to help restore proper
barrier function.
a
Active Micro Technologies, LLC
Market Intelligence
n According to Marie-Alice Dibon, PharmD, “Discovering the importance of
the microbiome is bringing about a small revolution in human health sciences.
It reminds us that everything is a question of ecosystem. In the same way that
humans evolve in an environment that we have to take into account not only for its
preservation but for our own sake, we realize that we ourselves are ecosystems of
our own and that we need to think in those terms when considering our health.”
Source: GCI (GCImagazine.com)

Research | C&T
From the research described thus far, it would not cides, etc. Although these preservatives all serve to
be surprising to find that HDAC also plays a key role protect the consumer, their mechanisms of action
in the immune and allergic response. However, its differ.3 Activities can range from preserving against
role in allergic skin inflammation is not entirely clear. multiple varieties of microorganisms, to different
One study from the Journal of Biological Chemistry strains of one common species. An adapted chart3
investigated HDAC and its involvement in the from the Journal of Applied Microbiology classifies
protective inflammatory pathway.14 Results indicated microbial susceptibilities to biocides, and provides a
that HDAC, specifically HDAC3, interacted with a useful guide for choosing the appropriate biocide for
specific surface cell protein, FCRI, which contributes a specific application.
to the protective functions of the immune system and As an example, this chart describes the Gram-
regulates the expression of a monocyte chemotactic positive bacteria Staphylococcus aureus, which has a
protein through various gene transcription pathways. relatively low resistance to biocides and is therefore
These findings suggest that HDAC could serve as a usually sensitive to effective use levels of antimicro-
major target for not only developing allergy therapeu- bial products. On the other hand, highly resistant
tics, but also reducing inflammation. This pertains to bacteria such as Gram-negative Providencis species
the cosmetic chemist because ultimately, a major goal are slightly more resistant and therefore may be
among personal care formulators is to eliminate or harder to kill or inhibit growth.
reduce inflammation as much as possible, especially Another example is triclosan, one of the most
when using effective levels of preservatives and effective biocides on the market. It is often used
biocides in cosmetic formulations. topically as a biocide in antimicrobial products,
rather than as a cosmetic preservative. Triclosan is
Preservative Mechanisms most often associated with hand sanitizers since it
Traditional biocides are used to preserve a wide has been the main active in them for more than 40
range of products, including cosmetics and personal years. Its use in the last 20 years has expanded to
care as well as foodstuffs and medicines. Examples soap, cosmetics and toothpaste.15 It is also found in
include disinfectants, antiseptics, pesticides, herbi- unexpected places; at some retailers, for instance,

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Untitled-1 1 3/27/15 11:59 AM

Research | C&T
grocery carts have incorporated it into the handles to time in a finished formula. In this case, two-month,
prevent bacteria growth. double challenge tests were performed using generic
Although effective, triclosan also has some cream formulas. Initially, products were inoculated
potentially harmful effects. It works by nonspecifi- with micro-organisms and decreases in inoculum
cally disrupting bacterial cell walls,4 which inevitably were recorded. After the first month, the products
results in the disturbance of the skin’s microflora bal- were re-inoculated and results were recorded again.
ance. As the present work will show, triclosan affects HDAC assay: An HDAC assay was used to screen
HDAC expression in keratinocytes, which denotes a four ingredients for their effects on HDAC activity as
negative impact on commensal microflora and skin a marker for skin microflora: the test antimicrobial
barrier function. peptide, triclosan, a paraben and phenoxyethanol
Considering these effects, along with continued blend, and Trichostatin A—a known HDAC inhibi-
demand for natural and sustainable ingredients, there tor—as a positive control. Serial dilutions of 1:2 were
are other approaches to consider. Natural antimi- used. This single-reagent-addition, homogenous,
crobial peptides are one example. These are typically luminescent assay is performed via a simultaneous
short chains of less than 50 amino acids, which are reaction that measures the relative activity of HDAC
synthesized via fermentation for different effects. enzymes from cells.16 The basic chemistry of this
Those acting in a protective manner secrete chemicals assay is depicted in Figure 2.
that are cytotoxic to pathogens; others act by a com- In brief, HDAC activity deacetylates a lumino-
petitive advantage, inhibiting and limiting the growth genic substrate,16 rendering it sensitive to a specific
of pathogens. In both cases, antimicrobial peptides proteolytic cleavage event that is mediated by the
are equipped to kill
pathogenic bacteria with
proven efficacy. However, Figure 2. Chemistry of the HDAC assay16
the question remained
as to whether they affect
HDAC activity. O O
O N N O N N
H OH OH
Materials and Boc-XX N
N S S HDAC Boc-XX NH
N S S
Methods O
H O
H
H HDAC Substrate
Minimum inhibitory N NH2
concentration (MIC) Developer
O
assays and challenge tests Reagent
were performed to test O
the efficacy of a specific N N
Luciferase OH
antimicrobial peptide “Glow-type”
(INCI: Leuconostoc/ luminescence ATP, Mg H2N S S
Radish Root Ferment

Filtrate). In addition, to
compare its effects with
synthetic preservatives
on skin microflora, an
Table 1. MIC Results for the Test Antimicrobial Peptide
assay using HDAC as a
marker was conducted.
MIC assay: MIC Microorganism MIC (ppm in final product) MIC (% in final product)
assays measure the E. coli 1.56 x 104
1.6
lowest concentration of S. aureus 3.13 x 104
3.1
an antimicrobial required P. aeruginosa 1.56 x 104 1.6
to inhibit the vis-
C. albicans 7.81 x 103
0.8
ible growth of a specific
A. niger 7.81 x 103
0.8
micro-organism after
incubation. Bacillus spp. 6.25 x 103 0.6
Challenge test: Salmonella spp. 6.25 x 103
0.6
Challenge tests evaluate Shigella spp. 6.25 x 103
0.6
an ingredient’s ability to Vibrio spp. 3.12 x 103 0.3
kill or prevent the growth
of microorganisms over

Untitled-1 1 3/27/15 11:54 AM
Research | C&T
reagent and liberates aminoluciferin. Free aminolucif- microbial sample, the more toxic it would be to cells
erin can then be measured using the firefly luciferase in regard to HDAC inhibition. This correlates with
reaction to produce a stable, persistent emission of the proper dilution factor of tested antimicrobials.
light that can be measured via colorimeter. All three It is important to note that these results cannot be
enzymatic events occur in coupled, homogeneous, compared with untreated media, as no HDAC activ-
nearly simultaneous reactions that reach a steady ity would be present. These findings confirmed the
state in 15–45 min.16 Essentially, more HDAC inhibi- antimicrobial peptide maintained HDAC levels best,
tion yields a lower luminescence value, signifying and thus would maintain microflora balance and
the most damaging antimicrobial as far as the skin overall skin health better than synthetic compounds
microbiome is concerned. such as triclosan and parabens.
Results
Regarding the MIC, 1-3% of the antimicrobial
peptide effectively inhibited the visible growth of the Table 3. HDAC Assay Results
nine microbes tested, as shown in Table 1. Results
of the challenge test, shown in Table 2, indicate all Ingredient Conc/Dil Luminscence
microbial growth was reduced by < 99.95%, which Trichostatin A 1.56 2132
is considered successful protection of the generic Peptide 32 2388
cream, according to PCPC limits. Also, as seen in
Paraben +
Table 3 and Figure 3, the results from the HDAC Phenoxyethanol 32 1539
assay indicate the antimicrobial peptide showed the Blend
best HDAC activity, with triclosan performing the
Triclosan 32 889.35
worst. The lowest concentration used is depicted
because the more concentrate/less dilute the anti-
Table 2. Challenge Results of the Test Antimicrobial Peptide
P. K.
S. aureus E. coli C. albicans A. niger B. cepacia
aeruginosa pneumoniae
Inoculum 2.02E 2.37E 2.33E 9.46E 2.97E 1.98E
2.79E + 06
level (initial) + 06 + 06 + 06 + 05 + 05 + 06
Day 0 (+)1.485% 5.485% 28.755% 39.535% 87.542% 6.810% >99.999%
Day 1 >99.999% >99.999% >99.999% >99.999% 90.404% >99.999% >99.999%
Day 2 >99.999% >99.999% >99.999% >99.999% 92.256% >99.999% >99.999%
Day 3 >99.999% >99.999% >99.999% >99.999% 94.108% >99.999% >99.999%
Day 7 >99.999% >99.999% >99.999% >99.999% 99.663% >99.999% >99.999%
Day 14 >99.999% >99.999% >99.999% >99.999% 99.663% >99.999% >99.999%
Day 21 >99.999% >99.999% >99.999% >99.999% 99.789% >99.999% >99.999%
Day 28 >99.999% >99.999% >99.999% >99.999% 99.987% >99.999% >99.999%
Inoculum
1.16E 2.57E 2.212E 7.03E 2.48E 2.18E
level 1.23E + 06
+ 06 + 06 + 06 + 06 + 05 + 06
(reinoculated)
Day 0 50.690% 38.132% 42.453% 37.127% 13.306% 7.317% >99.999%
Day 1 >99.999% >99.999% >99.999% >99.999% 17.339% >99.999% >99.999%
Day 2 >99.999% >99.999% >99.999% >99.999% 37.500% >99.999% >99.999%
Day 3 >99.999% >99.999% >99.999% >99.999% 84.879% >99.999% >99.999%
Day 7 >99.999% >99.999% >99.999% >99.999% 94.758% >99.999% >99.999%
Day 14 >99.999% >99.999% >99.999% >99.999% 96.371% >99.999% >99.999%
Day 21 >99.999% >99.999% >99.999% >99.999% 96.371% >99.999% >99.999%
Day 28 >99.999% >99.999% >99.999% >99.999% 99.113% >99.999% >99.999%
CT1505_Research_Danaher_fcx.indd 32 4/14/15 3:31 PM

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Untitled-1 1 3/27/15 11:58 AM

Research | C&T
Conclusions Figure 3. HDAC assay results
In this study, HDAC was
evaluated as a novel indicator
for skin microflora balance since
previous research has shown
that when this enzyme is altered
or reduced, skin’s commensal
microbiota, which protect
against unwanted microbes,
are less effective. The research
presented here proves that
some traditional biocides and
preservatives, although effective
antimicrobials, actually decrease
HDAC expression within
human skin cells. This could
lead to a compromised immune
defense system and overall
reduced skin health.
However, natural anti-
microbials provide a solution to balance effective with the HDAC enzyme as a model for the complex
preservation with maintenance of the skin’s natural nature of skin and the organisms that live there.
microbiome. This promotes the ultimate goal of elimi-
nating pathogenic microbes while maintaining skin’s References
protective microflora balance, in order to support 1. K Chiller et al, Skin microflora and bacterial infections of the skin,
overall skin health. More research should be per- J Inves Derm Symp Proceedings 6(3) 170–174 (2001)
formed in this field; however, there is ample promise 2. http://webdictionary.personalcarecouncil.org/jsp/Home.jsp

(Accessed Mar 27, 2015)
3. J-Y Maillard, Bacterial target sites for biocide action, J Applied
Microbio Symp Supplement 92 16S-27S (2002)
4. SP Yazdankhah et al, Triclosan and antimicrobial resistance in
bacteria: An overview, Microb Drug Resist 12(2) 83-90 (2006)
5. K Findley et al, Human skin fungal diversity, Nature 498 (7454)
367-370 (2013)
6. S Baron, Medical microbiology, U of Tex Medical Branch at
Galveston 4, ch 6 (1996)
7. E Grice et al, Topographical and temporal diversity of the human
skin microbiome, Science 324(5931) 1190-1192 (2009)
8. www.genome.gov/dmd/img.cfm?node=Photos/
Graphics&id=85320 (Accessed Mar 27, 2015)
9. www.the-scientist.com/?articles.view/articleNo/40228/title/
Microbes-of-the-Skin/ (Accessed Mar 27, 2015)
10. www.the-scientist.com/?articles.view/articleNo/40600/title/The-
Body-s-Ecosystem/#skin (Accessed Mar 27, 2015)
11. T Akimova et al, Histone/protein deacetylases and T-cell immune
responses, Blood J 119(11) 2443-2451 (2012)
12. E Robertson et al, ARNT controls the expression of epidermal
differentiation genes through HDAC- and EGFR-dependent
pathways, J Cell Sci 125 3320-3332 (2012)
13. T Alenghat et al, Histone deacetylase 3 coordinates commensal-
bacteria-dependent intestinal homeostasis, Nature 504 153-157
(2013)
14. K Youngmi et al, histone deacetylase 3 mediates allergic skin
inflammation by regulating expression of MCP1 protein, J Biol
Chem 287(31) 25844-25859 (2012)
15. C Cooney, Triclosan comes under scrutiny, Envt Health Persp
118(6) A242 (2010)
16. www.promega.com/~/media/files/resources/protocols/techni-
cal%20manuals/101/hdac%20glo%20i%20ii%20assay%20
and%20screening%20system%20protocol.pdf (Accessed Mar
27, 2105)

Untitled-3 1 4/7/15 3:43 PM
Research | C&T
Silica Nanoparticles for

Increased Cosmetic
Ingredient Efficacy*
S. Nafisi, PhD and H. I. Maibach, MD
University of California, San Francisco
S
kin is a unique barrier composed of highly organized and heteroge-
KEY WORDS neous layers, including appendages such as hair follicles and sweat
and sebaceous glands. It consists of three layers; from outside to
silica nanoparticles • inside: the epidermis, dermis and hypodermis. The outermost layer of the
percutaneous penetration • epidermis is the stratum corneum (SC), to which the main barrier function
cosmetic ingredients • of skin is attributed. Skin keeps chemicals and pathogens from entering the
drugs • toxicity body, protects against sunlight and retains the body’s water-rich internal
organs from drying out by preventing water loss, especially in dry environ-
ments (see Figure 1 on Page 38).1
Recently, the use of nanoparticles has become widespread to increase the
penetration of compounds into skin. Nanoparticles are commonly defined
as 1 nm to 100 nm in size, and have at least one dimension on this nano-
ABSTRACT scale.2 Those that are 40 nm or smaller in diameter have been successful in
Nanotechnology is a penetrating skin.3 Silica nanoparticles (SNPs) in particular have attracted
rapidly expanding area of significant interest as cosmetic ingredients and for drug delivery, due to
research for developing unique properties such as their hydrophilic surface; the versatility of silane
science-based solutions chemistry for surface functionalization; the ease and relatively low cost of
their large-scale synthesis; and their excellent biocompatibility.4 SNPs may
for innovative therapeutics.
offer revolutionary treatment for several skin diseases by controlling the
Recently, silica sustained release of cosmetic ingredients or drugs to the skin, as well as
nanoparticles (SNPs) have enhancing the skin penetration of encapsulated ingredients. They are also
emerged in cosmetics candidates for skin cancer therapy, transcutaneous vaccination, and gene
and dermal preparations, delivery. Further, they can act as carriers for drugs having low solubility,
offering revolutionary and they may improve drug safety, stability and performance.5, 6 Following
application by controlling is a review of their chemistry, along with potential applications, toxicology
the sustained release of considerations and future perspectives on their use.
cosmetic ingredients and/ Silica Chemistry
or drugs and enhanced Silicon dioxide, also known as silica, is an oxide of silicon with the
skin penetration. chemical formula SiO2. It is the most common element found in nature.
Silica can be divided into the main two classes: crystalline and amorphous.
Crystalline micron-sized silica is a basic component of soil, sand, granite
and many other minerals; amorphous silica is synthetic except for biogenic
Save to
My Library
*Adapted from S Nafisi, M Schaffer Korting and HI Maibach, Perspectives on percutaneous penetration:
Silica nanoparticles, Nanotoxicology (in press)

CT1505_Research_Dermview_fcx.indd 36 4/13/15 12:02 PM

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Untitled-1 1 4/3/15 3:47 PM

Research | C&T
diatomaceous earth, which is composed of particles be controlled by tuning the composition and concen-
or structural units less than 1 μm in diameter. tration of surfactants during synthesis.5, 6
Synthetic amorphous (non-crystalline) silica particles Nonporous silica nanoparticles: Nonporous
are found in different forms7 (see Table 1 on Page 40), silica nanoparticles or monodisperse silica spheres
three of which have potential in topical skin care were firstly prepared by the Stöber production
treatments and cosmetics. These include pyrogenic process. Their biomedical applications for therapy
or fumed silica, non-porous silica nanoparticles and and diagnosis are categorized based on the actives
mesoporous silica nanoparticles. they deliver; e.g., small-molecule drugs, proteins or
photo sensitizers; genes; or different contrast agents
for molecular imaging. Nonporous SNPs can deliver
SNPs can be used as their cargo through encapsulation or conjugation.5
Mesoporous silica nanoparticles: Mesoporous
penetration enhancers, silica nanoparticles (MSNs) having a uniform pore
size and long-range, ordered pore structure, were first
which help to promote reported in the early 1990s using different alkyl chain
lengths of cationic surfactants such as dodecyltri-
drug diffusion through methylammonium or hexadecyltrimethylammonium
ions as structure-directing agents (SDAs).
the SC to the viable The abundant availability of various surfactants
and a deep understanding of sol-gel chemistry have
epidermis and dermis. enabled the development of ordered MSNs with dif-
ferent structures, such as Mobil Crystalline Materials
(MCM) and Santa Barbara Amorphous (SBA) types.
Pyrogenic or fumed silica: Pyrogenic or fumed SBA has thicker pore walls and wider pore sizes, i.e.,
silica has an extremely low bulk density and a high 5 nm to 30 nm, than MCM. Until now, most research
surface area. It is a readily emulsifiable powder and on drug delivery and cancer therapy applications of
has excellent dispersion properties and compatibility ordered MSNs are based on MCM-41 and SBA-15.
with other ingredients. It is used as a rheological These have been synthesized as ordered or hollow/
additive in personal care products such as face rattle-type mesoporous silica structures, and they are
powder, rouge, eye shadow, mascara and cosmetic widely used for the delivery of active payloads based
pencils. It also enables high pigment levels in cosmet- on physical or chemical adsorption.6
ics by preventing re-agglomeration of the pigments.
Another advantage of fumed silica is its low sensitiv- Continued on Page 42
ity to temperature, electrolytes
and pH.
In formulations, it coun- Figure 1. Simplified diagram of the skin and routes of
teracts oily or greasy skin penetration
feel, and its particles create
stable Pickering emulsions.
In sun care emulsions, it can
improve water resistance,
and hydrophobic grades can
produce a more homogeneous
distribution of physical and
chemical UV filters, raising
the SPF. In lipsticks and nail
polish, fumed silica improves
the homogeneous distribution
of pigments and prevents them
from settling. It is also nontoxic
and a non-irritant.8
Based on biomedical
applications, silica NPs can be
classified as mesoporous or
nonporous. Furthermore, the
size and shape of silica NPs can

Untitled-1 1 4/8/15 10:23 AM
Silica Forms Synthesis Method Size Surface Area Applications Reference
1. Manufacture of glass, abrasives,
Crystalline na 0.5-3.0 µm 9.4 m2/g ceramics, enamels, scouring, Iier 1979; Unger 1979
silica castings in molds
2. 2.1.
Filtration agent, abrasive, absorbent, Iier 1979; ECETOC 2006;
Amorphous Natural na 0.5-2.0 µm High porosity
CT1505_Research_Dermview_fcx.indd 40
industrial filler IMA Europe 2014
Research | C&T
silica amorphous
2.2. 50–600 m2/g Counteracts oily or greasy skin feel,

2.2.1.
Synthetic Non-porous raises sun protection, improves storage, Iier 1979; Willey 1982;
Pyrogenic or Thermal process 5-50 nm
amorphous Low bulk stabilizes emulsions temperature and ECETOC 2006
Table 1. Different Forms of Silica
fumed silica
(SAS) density stability
40 | www.CosmeticsandToiletries.com
Rubber and plastics, cleaning,
2.2.2. thickening, polishing agent in
Precipitated 30-500 m2/g toothpastes, food processing,
Wet process 5-100 nm Iier 1979; ECETOC 2006
amorphous Porous pharmaceuticals additive for
silica anti-caking, absorbent, antiblocking
agentin polymer films
Abrasives in carbonless papers, fining
agent and catalysis, desiccant,
2.2.3. 800 m2/g stationary phase in chromatography, Iier 1979; ECETOC 2006;
Wet process 30-100 nm
Silica gel Porous anti-caking agent, filter aid, emulsifying IMA Europe 2014
agent, viscosity control agent,
anti-settling agent
Non-porous
2.2.4. Stober and Fink 1968;
50-2,000 nm and porous Masks in lithography, optical sensor,
Nonporous Different synthesis Zhang et al., 2000;
Controllable Controllable drug delivery, gene delivery, molecular
silica nano- methods Xia et al., 2000;
sphere size surface imaging
particles Tang and Cheng, 2013
properties
Surface area Tang et al., 2012;

> 1,000 m2/g Confined-space catalysis; acoustic, Slowing et al., 2010;
2.2.5.
2-50 nm Porous, high thermal and electrical insulation; Wan and Zhao 2007;
Mesoporous
Different synthesis Controllable pore volume enzyme immobilization; drug delivery Hoffman et al., 2006;
silica
methods pore size, 0.5-2.5 cm3/g system; cell marker; gene transfection Garcia-Bennett, 2011;
nanoparticles
morphology High drug reagents; imaging modality; bone tissue Vallet-Regi et al., 2007
(MSN)
loading regeneration Lou et al., 2008;
capability Liu et al., 2011
2.2.6.
Silica host for na na na Medical imaging; drug delivery Piao et al., 2008
other NPs
Vol. 130, No. 4 | May 2015
4/14/15 3:41 PM
Untitled-1 2 4/3/15 4:12 PM
Research | C&T
Potential Applications and remarkable improvement in sunscreen photostabil-
Ongoing Research ity.14 In other work, the inclusion of a water-soluble
analog of vitamin E, Trolox, in the MCM-41 matrix
As noted, SNPs can be used as penetration
slowed its in vitro release and increased the pho-
enhancers, which help to promote drug diffusion
tostability for the complexed agent, particularly in
through the SC to the viable epidermis and dermis.
o/w emulsions. Importantly, the radical-scavenging
In one study, SNP-coated submicron o/w emulsions
activity of it also was maintained after immobiliza-
were shown to increase the stability and skin penetra-
tion.15 Finally, caffeine loading in SNPs resulted in
tion of lipophilic agents, retinol and the fluorescent
the formulation of both core-shell and multilayered
dye acridine orange 10-nonyl bromide. Lecithin and
caffeine-silica structures, reducing and delaying the
oleylamine addition, respectively, were used for the
permeation of caffeine into pig skin, in comparison
induction of negative and positive charges to the
with a reference gel, independently from the amount
emulsion. Both formulations improved: retinol resis-
of the tested formulation.16
tance to UV-induced degradation, control of release,
The toxicity of SNPs depends strongly on their
and the penetration of both agents into excised
physicochemical properties, such as particle size,
porcine skin, as compared with a free agent control.9, 10
shape, porosity, chemical purity and solubility.5, 6
In a separate study of human volunteers, the
Surface area also plays a crucial role in toxicity due to
addition of monodisperse silica spheres (~486 nm
interfacing with biological milieu.
diameter) to an emulsion significantly increased
quercetin penetration into the SC.11 In relation,
complexes of quercetin with plain or octyl-function-
Conclusions and
alized MCM-41 increased emulsion stability without Future Perspectives
undermining the antioxidant efficacy of quercetin, SNPs are promising for the delivery of cosmetic
thus suggesting an innovative use for such mesopo- ingredients and topical therapies, as they exhibit
rous composite materials in skin care.12 Moreover, many advantages such as having highly controllable
in another study, the immobilization of rutin in size, surface chemistry and shape. They are already
the pores of an aminopropyl silica (NH2-MCM-41) finding application in the delivery of cosmetic ingre-
stabilized it against UV degradation and enhanced its dients, drugs, proteins and genes, and for molecular
accumulation in porcine skin ex vivo while maintain- imaging. However, before SNPs can be used routinely,
ing its antioxidant properties.13 some major challenges must be overcome. These
In relation to photostability and safety, a differ- include the need to improve their ingredient/drug
ent study trapped octyl methoxycinnamate within loading, spatial and temporal control of drug release,
the pores of the mesoporous silicate MCM-41, pore targeting to diseased sites, scalable manufacturing
openings were plugged, and the loaded nanoparticles and long-term stability. Also, their biocompatibility
were incorporated into a lipid-based cosmetic formu- and potential toxicity remain sine qua nons, requiring
lation. This provided broader photoprotection and a accurate penetration assessments for absorption, dis-

tribution, metabolism and excretion. Further details 8. JP Hewitt, Formulating with nanotechnology in skin care oppor-
tunities and challenges, in Nanotechnology in Dermatology, A
of the current knowledge and future opportunities for Nasir, A Friedman and S Wang, eds, Springer, New York (2012)
these assessments can be found elsewhere.17 Finally, pp 1-8
organo-silica hybrid NPs, having the unique proper- 9. N Ghouchi-Eskandar, S Simovic and CA Prestidge, Chemical
stability and phase distribution of all-trans-retinol in nanoparticle-
ties of SNPs but functionalities introduced by organic coated emulsions, Int J Pharm 376 186-194 (2009a)
functional groups, could provide more sophisticated 10. N Ghouchi-Eskandar, S Simovic and CA Prestidge, Nanoparticle
silica-based nanomedicines, with highly controllable coated emulsions as novel dermal delivery vehicles, Curr Drug
drug loading and responsive drug release. Deliv 6 367-373 (2009b)
11. S Scalia, E Franceschinis, D Bertelli and V Iannuccelli, Compara-
tive evaluation of the effect of permeation enhancers, lipid
References nanoparticles and colloidal silica on in vivo human skin penetra-
tion of quercetin, Skin Pharmacol Physiol 26 57-67 (2013)
1. http://ec.europa.eu/environment/chemicals/nanotech/faq/defini-
tion_en.htm (Accessed Mar 16, 2015) 12. G Berlier, L Gastaldi, E Ugazio, I Miletto, P Iliade and S Sapino,
Stabilization of quercetin flavonoid in MCM-41 mesoporous
2. MR Prausnitz et al, Skin barrier and transdermal drug delivery,
silica: Positive effect of surface functionalization, J Colloid
in Dermatology, J Bolognia, JL Jorizzo and JV Schaffer, eds,
Interface Sci 393 109-118 (2013a)
Saunders/Elsevier, Atlanta (1) ch 124 (2012) pp 2065-2073
13. G Berlier et al, MCM-41 as a useful vector for rutin topical for-
3. CA Poland, SAK Read, J Varet, G Carse, FM Christensen and
mulations: Synthesis, characterization and testing, Int J Pharm
SM Hankin, Dermal absorption of nanomaterials. The Danish
457 177-186 (2013b)
Environmental Protection Agency, Environmental Project No.
1504, Denmark (2013) 14. V Ambrogi, L Latterini, F Marmottini, C Pagano and M Ricci,
Mesoporous silicate MCM-41 as a particulate carrier for octyl
4. II Slowing, JL Vivero-Escoto, CW Wu and VSY Lin, Mesoporous
methoxycinnamate: Sunscreen release and photostability,
silica nanoparticles as controlled release drug delivery and gene
J Pharm Sci 102 1468–1475 (2013)
transfection carriers, Adv Drug Deliv Rev 60 1278-1288 (2008)
15. L Gastaldi, E Ugazio, S Sapino, P Iliade, I Miletto and G Berlier,
5. L Tang and J Cheng, Nonporous silica nanoparticles for nano-
Mesoporous silica as a carrier for topical application: The Trolox
medicine application, Nano Today 8 290-312 (2013)
case study, Phys Chem Chem Phys 14 11318-11326 (2012)
6. F Tang, L Li and D Chen, Mesoporous silica nanoparticles:
16. M Pilloni et al, Drug silica nanocomposite: Preparation, charac-
Synthesis, biocompatibility and drug delivery, Adv Mater 24
terization and skin permeation studies, Pharm Dev Technol 18
1504-1534 (2012)
626-633 (2013)
7. RK Iier, The Chemistry of Silica, John Wiley and Sons, New York
17. S Nafisi, M Schaffer Korting and HI Maibach, Perspectives on
(1979)
percutaneous penetration: Silica nanoparticles, Nanotoxicology
(in press)

Untitled-2 2 4/13/15 3:45 PM
Untitled-2 3 4/13/15 3:45 PM
Testing | C&T
Defining and
Controlling Frizz
Trefor Evans, PhD
T.A Evans Inc., Princeton, NJ USA
H
air scientists must always remember, while potentially biting their
KEY WORDS tongues, that hair care products are sold to the general public using
“consumer language.” Consumers use a number of descriptors and
frizz • alignment • terms to communicate their hair’s properties and needs, and a collection of
humidity • conditioner • these expressions has become the lexicon of the beauty industry. However,
static flyaway • water-set scientists should take these descriptors with a pinch of salt and carefully
consider the true causes of issues, as there is danger in taking these con-
sumer expressions literally. By means of illustration, earlier articles in this
series described how the consumer term moisturization has no relationship
to the technical water content of hair,1, 2 while strengthening claims are
relatively common on products that produce no enhancement of tensile
ABSTRACT properties.3, 4 Some consumer terms do have logical scientific counterparts.
There is likely a variety of For example, conditioning equates relatively well to surface lubrication,1, 5
albeit in an aesthetically pleasing manner.
causes and contributors
However, others are distinctly more nebulous. One such imprecise term
to the nebulous consumer
is the consumer word frizz. This article begins by crafting a reasonable
term “frizz.” This article definition for this consumer term and subsequently describes methodolo-
attempts to craft a gies that may be used to demonstrate positive benefits associated with the
universal definition and product forms in mitigating this occurrence.
then progresses to further
examine impacting factors. Defining Frizz
These discussions focus The definition of frizz is not straightforward, so it is perhaps easier
on methods for quantifying to define what frizz is not. Namely, highly aligned, bone-straight hair is
clearly devoid of any frizziness. In this orderly state, hair appears sleek and
hair properties and
smooth, is shiny, and possesses a fluid flowing motion; yet all these desir-
assessing the positive able attributes arise from the same underlying property—a very high degree
impact of commercial hair of fiber alignment. Therefore, it seems reasonable to suggest that complaints
care products. relating to frizz involve an inability to reach this sought-after condition, or
some partial loss of this state after an initial degree of success.
In testing this definition, it is necessary to contemplate various reasons
for fiber misalignment. Most obvious is the natural shape of the hair, where
kinky African hair possesses no alignment and is frequently described as
frizzy. With this said, curly hair is not inherently frizzy, with well-defined
Save to curls consisting of highly-aligned fiber arrangements. Brushing or combing
My Library
hair in a low-humidity environment will lead to the generation of static
flyaway—another condition commonly termed frizz. Meanwhile, at the

CT1505_Testing_Evans_fcx.indd 46 4/13/15 2:26 PM

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Untitled-1 1 4/3/15 3:53 PM

Testing | C&T
other end of the spectrum, high-humidity conditions a seminal paper by Lunn and Evans6 in 1977, and
can quickly destroy temporary alignment attained Figure 1 shows the author’s design for a modern
through heat styling, and the result is again generally automated approach for quantifying this property.
termed frizz. It is suggested that hair’s condition/ Hair tresses are brushed in a highly reproducible
health can also be a contributor, in that broken fibers manner with a rotating motorized arm while a specif-
fray and produce split ends that often protrude due ically positioned sensor measures the resulting charge
to length differences relative to their neighbors. In build-up. The apparatus is small enough to be housed
higher numbers these shorter, deformed fibers may inside a benchtop humidity chamber to ensure
also constitute a frizzy appearance. As such, this controlled and constant atmospheric conditions.
proposed definition appears to hold up to scrutiny. Figure 2 shows a set of typical results for hair treated
with commercially available 2-in-1 shampoo and
Conditioners to the Rescue conditioner products, relative to an unconditioned
Traditional hair conditioner products are able control. Both product forms demonstrate a positive
to help with most frizz issues. A previous article effect in slowing this occurrence, with the condi-
described how the use of such products produces tioner performance being especially noteworthy.
a dramatic reduction in hair breakage during the
grooming process. This occurs because surface lubri-
cation lowers snagging and tangling during brushing Figure 1. Custom-built device for
or combing, which then reduces the fatiguing forces measuring static build-up on hair
experienced by individual hair fibers. In practice,
this occurrence is convincingly demonstrated by
performing repeated grooming experiments where,
as the name suggests, hair tresses are continuously
combed or brushed with periodic counting of broken
fibers. Through this approach, it is not uncommon
for the use of conventional, rinse-off conditioners to
lower hair breakage by 70% to 80%, while leave-in
treatments may produce greater benefits.
Low-Humidity Frizz Issues

Conditioner products are also extremely effective
at lowering static electricity build-up during groom-
ing. The underlying cause of this problem involves
the migration of electrons from one body to another
when objects are rubbed together.
The nature of this electron flow is
dependent on the relative positioning Figure 2. Reduction of static build-up as a result of
of materials in the triboelectric series, treatment with commercial 2-in-1 and conditioner products
and during grooming, electrons will
travel from hair to comb/brush with
the subsequent development of a
positive charge on individual fibers.
Thus, unruly static flyaway occurs
due to electrostatic repulsion between
strands with the same surface charge.
The lifetime of this surface charge is
dependent on the ease by which it can
be conducted away, which strongly
depends on the moisture content of
the hair. Therefore, charge dissipation
is poorest under low-humidity condi-
tions, where hair contains lesser water
content,2 and static flyaway problems
are much more likely to occur.
The groundwork for measuring
static build-up in hair was given in

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Untitled-1 1 4/7/15 3:40 PM

Testing | C&T
With this said, there is some dispute in the water, and consequently, wet hair is less structured
scientific literature as to the mechanism by which and more pliable.
products produce this benefit. Lunn and Evans6 In essence, heat styling devices drive water from
suggested that surface lubrication leads to less charge the hair, inducing additional internal structuring
build-up, while Jachowicz et al.7 believed that cationic which can be sufficient to anchor hair in a new
surfactant deposition increases surface conductivity temporary conformation. The water content of hair
and thus facilitates charge dissipation. A further sup- will progressively re-equilibrate to a level commen-
position is that the presence of these surface deposits surate with the relative humidity of the surrounding
changes the position of hair in the triboelectric series environment2 and consequently, the style will relax
and thus influences the extent of charge build-up and gradually revert to its natural conformation. The
in a different manner. None of these explanations is rate and extent of style loss will be proportionate to
mutually exclusive, and it is entirely possible that effi- the climatic conditions. For example, hot, humid
cacy involves some contribution of all three factors. summer days lead to especially rapid style deterio-
High-Humidity Frizz Issues

The shape of hair can be temporarily altered by Market Intelligence
allowing it to dry in a specific conformation, and
this occurrence is commonly termed a water-set. The n When shopping for products, women with wavy
process relates to the internal structure of hair being or curly hair identify fighting frizz as the biggest
provided by two different types of chemical bonds. consideration.
Permanent structure is attained through covalent cys-
tine disulfide bonds within the keratin protein, while n Only 9% of coily-haired women cite fighting frizz
hydrogen bonding between oppositely charged amino as their biggest concern, compared to 48% of
acid groups produces additional secondary structur- wavy-haired consumers.
ing in the dry state. However, these electrostatic Source: GCI (GCImagazine.com)
interactions are disrupted by the solvating power of

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Untitled-1 1 4/3/15 3:55 PM

Testing | C&T
ration. As a result, consumers with wavy or curly The effectiveness of these products can be
hair, who use this approach to create sleek, straight demonstrated in the laboratory. Anti-frizz experi-
styles, will complain about “frizz” as this reversion ments typically involve the use of high-quality digital
process occurs. photography in combination with image analysis
“Anti-frizz” products have become prevalent approaches to visualize and quantify the shape of
on hair care shelves in recent years. These are often hair tresses. Figure 3 shows Mulatto hair tresses
traditional leave-in conditioner products, although suspended in a benchtop environmental chamber.
a somewhat newer product form involves serums After capturing images to document this initial state,
that consist of various oils. It is often presumed that the hair is straightened using a conventional, com-
hydrophobic deposits from such products give rise mercially available heat-styling device; needless to
to an occlusive surface layer that inhibits moisture say, this critical step must be performed in a highly
adsorption. However, this appears unlikely, as water is controlled and reproducible manner. Additional
a small molecule whose pathway is difficult to deter. photographs are then taken to characterize the
Nonetheless, consumer acceptance of such products straightened state of the tress, and the relative humid-
suggests some manner of technical efficacy. ity is raised to some elevated level with further image
collection to document the reversion process with
time. Figure 4 illustrates this progressive frizzing of
Figure 3. Experimental set-up for the hair.
performing anti-frizz measurements
Frizz is associated
with one common
property—fiber
misalignment.
Results do show the ability for certain hair treat-

ments to slow down this reversion rate to varying
degrees. Clearly, products containing styling fixatives
tend to yield the most enduring benefit, yet cohe-
sion between fibers or simply the additional weight
imparted by surface deposits would also seem to be
contributors to this efficacy.
Summary
Frizz is a nebulous consumer term with a number
of potential causes. Yet, it is hoped that the definition
suggested here provides an underlying commonality
behind the different ways in which this expression
Figure 4. Progressive reversion of is commonly used. Namely, it is postulated that frizz
involves an inability to achieve a desired state of high
straightened hair upon exposure to
hair fiber alignment or some loss of this state after a
elevated humidity
degree of initial success. Accordingly, this definition
encompasses issues associated with high-humidity
conditions (water-set reversion), low-humidity
conditions (static flyaway) and hair damage (split
ends), while also accounting for the innate properties
of hair itself. The good news is that conventional,
commercially available conditioners are able to help
with most of these issues. Surface lubrication lowers
grooming forces, which subsequently reduces the
incidence of snags and tangles and thus produces
a dramatic reduction in fiber breakage. This same

lubrication, perhaps in combination with improved provide similar efficacy in terms of reduced breakage,
surface conductivity and a re-positioning within the retarding static electricity build-up and weighing
triboelectric series, greatly reduces static electricity down unruly hair. There is also a popular belief that
buildup during brushing or combing of hair with low such treatments afford a degree of protection to the
water content. Moreover, increased weight associ- hair during high temperature styling. This hot topic
ated with surface deposits can provide some help of heat protection will be covered in the next edition
in slowing the reversion of straightened hair under of this column.
high-humidity conditions.
In general, anti-frizz products tend to be heavier References
conditioners that are often used in a “leave-in” man- 1. TA Evans, Consumer vs. scientific language: Relating in vivo to
ner, as opposed to being partially rinsed out. These in vitro, Cosm & Toil 128(5) 300-304 (2013)
products may be too heavy a coating for consumers 2. TA Evans, Measuring the water content of hair, Cosm & Toil
129(2) 64-69 (2014)
with fine hair, but they can be lavishly applied to
3. TA Evans, Measuring Hair Strength, Part 1: Stress-strain curves,
thicker, curly hair to yield considerable benefits. A Cosm & Toil 128(8) 590-594 (2013)
second popular product form is a mixture of non-vol- 4. TA Evans, Measuring Hair Strength, Part 2: Fiber Breakage
atile oils that are often contained in a cyclomethicone Cosm & Toil 128(12) 854-859 (2013)
base. In this case, the volatile silicone can evaporate 5. TA Evans, Evaluating Hair Conditioning with Instrumental Comb-
ing, Cosm & Toil 126(8) 558-563 (2011)
over time to reduce the extent of surface coating.
6. AC Lunn and RE Evans, The electrostatic properties of human
Oiling of hair is a popular and long-standing practice hair, J Cosmet Sci 28 549-569 (1977)
in a number of cultures, and this process appears 7. J Jachowicz, G Wis-Surel and GL Garcia, Relationship between
to have attained current attention and acceptance triboelectric charge and surface modifications of human hair,
J Cosmet Sci 36 189-212 (1985)
as a corollary of the recent trend for sleek styles.
Accordingly, a flood of exotic-sounding oils have
been introduced to the market, perhaps in response
to the remarkable popularity of argan oil. Of course,
these products also lubricate the hair and therefore

Testing | C&T
Sea Anemone Delivery of

Collagen and γ-PGA for
Anti-aging Benefits
Yossi Tal, PhD, Einav Danon and
Amir Toren, PhD
StarletDerma Ltd., Caesarea, Israel
Alain Khaiat, PhD
Seers Consulting, Singapore
T
he skin is a formidable barrier, protecting the body’s inner organs.
KEY WORDS Therefore, delivering therapeutic substances into it for anti-aging ben-
efits is a challenge. In particular, preferred anti-aging actives include
anti-aging • delivery •
collagen, for restructuring skin, and poly-γ-glutamate (γ-PGA)—a natural,
submicron injection nontoxic peptide polymer recognized1 in skin care for its moisturizing2, 3
system • marine collagen • and anti-aging4 properties. However, topical collagen and γ-PGA molecules
poly-γ-glutamate • are generally too large to penetrate the dermis and therefore have limited
microcapsule • nematocysts effects in stimulating the synthesis of new collagen in the skin.
These challenges were the focus of the current study, in which a natural
microinjection system from the stinging cells of the Cnidaria phylus sea
ABSTRACT
anemone was developed to effectively puncture the stratum corneum (SC)
The effective delivery layer and deliver both marine collagen and γ-PGA into skin. Described here
of youth-preserving is the rationale behind the ingredient choices and delivery mechanism, as
collagen and moisture well as tests to determine the efficacy of the approach.
remains a cosmetic Holy
Grail. In response, this
Marine Collagen
Collagen is a fibrous protein that acts as the main structural component
study describes a natural
of the skin’s dermal layer. Its fibers wield mechanical strength and provide
microinjection system support and elasticity to the skin, as well as to the majority of proteins in
based on the stinging cartilage, bone, tendons and ligaments. Skin aging is associated with an
cells of the Cnidaria sea increasing imbalance between the breakdown and assembly of collagen; i.e.,
anemone to effectively collagen degradation is accelerated while collagen synthesis is decreased.5
puncture the stratum Damage induced by exposure to the sun’s ultraviolet (UV) rays magnifies
corneum layer and deliver this process.6
its content—both marine While the collagen used in cosmetic formulations is often mammalian-
derived,7 there is a growing concern over viral agents from this source
collagen and γ-PGA—into
causing degenerative neurological disorders.8 However, a novel, safe and
skin, offering a promising
sustainable alternative is the collagen produced by marine organisms,
new class of solutions to which can be manufactured from sea anemone using an environmentally
age-old challenges. friendly recirculatory aquatic system. Marine collagen has a wide range of
properties. Its antioxidant benefits have been applied in skin care to prevent
damage caused by UV rays and low humidity, which increases TEWL and
Save to reduces barrier function.
My Library
Topical marine collagen is known as a naturally rejuvenating substance
that replenishes the body’s own collagen supply, providing nutrients to

CT1505_Testing_Toren_fcx.indd 54 4/14/15 3:45 PM

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Untitled-1 1 3/27/15 11:53 AM

Testing | C&T
rebuild collagen types I and III cells.8 Previously, applying a layer onto skin. One would contain a
it was demonstrated that by adding collagen to formula incorporating the microinjectors, and the
cosmetic emulsions, structural processes and other, a water-based formulation. Upon application,
moisturizing effects were enhanced in the skin in a the system would activate by water from the second
limited manner, depending on the bioavailability of chamber flowing through the porous walls of the
the collagen. Furthermore, like mammalian collagen, microcapsules in the formula from the first chamber,
marine collagen can be used as a raw material for the causing dissociation of the large, aggregated matrix
production of cosmetic fillers.9 of γ-PGA trapped within. This in turn increases the
osmotic pressure, resulting in the ejection of the
submicronic collagenic needle. Thus, the γ-PGA
This sea anemone matrix serves as the internal “battery” of the system
and, together with the high tensile strength of the
source for collagen also microcapsule wall, can build up the pressure required
to propel the submicronic needle at speeds high
provides an epidermal enough to puncture the skin and immediately deliver
the microcapsule content of collagen and γ-PGA.
delivery platform via The ability of this system to effectively punc-
its natural submicron ture the SC and deliver both marine collagen and
γ-PGA to target areas, increasing skin collagen and
injection system. enhancing skin rejuvenation, was therefore inves-
tigated. Methods including Raman spectroscopy
and high-performance liquid chromatography
(HPLC) were used to assess the depth of penetration,
Delivery Mechanism quantify delivery and verify collagen and γ-PGA
The same sea anemone source for collagen also epidermal content.
provides an epidermal delivery platform that allows
collagen to penetrate the skin: the natural submicron Materials and Methods
injection system of this nematocyst5—i.e., microcap- Preparation of microcapsules: Intact microcap-
sules made of collagen and γ-PGAa from its stinging sules were isolated as previously described by Tal et
cells or cnidocysts. The fundamental principle is al.,10 with minor modifications. Briefly, specimens of
based on active delivery. The isolated microcapsules, the Nematostella vectensis starlet sea anemone were
although no longer a part of a living cell, retain their collected and kept frozen before microcapsule extrac-
ability to “fire” contained materials. They engender a tion. The anemones were homogenized in 12.5 ppt
high internal pressure of 150 bars and are activated artificial seawater—their medium of cultivation—fol-
by water, resulting in the discharge of long, folded lowed by two centrifugations to differentiate between
collagenic needles at an ultrafast acceleration of the relatively dense, intact microcapsules; discharged
5 × 106 g. Due to their small size and the speed at microcapsules; and cell debris. The isolated puri-
which they are fired, the collagenic needles painlessly fied microcapsules were washed with decreasing
penetrate the skin without the use of external energy concentrations of NaCl and CaCl2 to a final salinity
sources or artificial chemicals. of 15 mM NaCl and 0.2 mM CaCl2, and immediately
This discharge is controlled by osmotic bal- freeze-dried. The microcapsules were then stored in a
ance. Product concepts based on this system would powder form at 2°C to 8°C until use.
therefore be packaged in two chambers, each γ-PGA content in microcapsules: To quantify the
γ-PGA content in microcapsules, a specific analytical
a
InoCyte (INCI: Sodium Polygamma-Glutamate (and) Collagen), method was developed. Briefly, 20 mg of the micro-
StarletDerma, Ltd.
capsule powder were activated in 1 mL of double
distilled water (DDW), filtered at 0.22 µM, and
Market Intelligence analyzed by HPLC for its γ-PGA vs. a γ-PGA stan-
dard solution. These analyses indicated that 38.3 µg
n The desire for truly natural products will continue
of γ-PGA are expelled upon activation of 20 mg of
to propel the global natural personal care industry.
microcapsules.
This segment’s growth is projected at a CAGR of
Epidermal delivery of dye: Porcine ear skins
slightly less than 10% through 2019, according to
were covered with microcapsules in a test gel (see
Kline & Company.
Formula 1), and 0.05% toluidine blue dye solution
Source: GCI (GCImagazine.com) was then added. After 5 min, the treated sites were
rinsed with distilled water, gently wiped to remove

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Untitled-1 1 4/14/15 3:55 PM

Testing | C&T
the applied materials, and photographed. To examine control, skinb pieces were covered with the same gel
dye permeability, the skin was tape-stripped 30 times excluding the microcapsules and overlaid with water.
to remove the SC and the residual skin was photo- During the experiment, 1-mL samples were taken
graphed under a microscope. from the receiver compartment at predetermined
Microcapsule penetration depth: Penetration times and after each withdrawal, the receiver was
into skin was evaluated using a confocal Raman filled with fresh saline solution.
spectrometer since this instrument can measure the The samples were analyzed by HPLCc with a diode
diffusion of molecules non-invasively. Pig skin was array detector. The analysis was performed at room
placed in a Franz flow cell system between the lower temperature using a 5-mm columnd. The mobile
and upper compartments. Buffer was used as a solu- phase consisted of: 68% acetonitrile (20%) in 20 mM
tion in the lower compartment, and a thin, 25-μL/ of pH 6 phosphate buffer; and 32% acetonitrile.
cm2 layer of the microcapsule materiala in the same b
Epiderm 606-X, MatTek
test gel (see Formula 1) was placed on air-dried skin, c
LC1090 Liquid Chromatograph, Hewlett Packard
then activated using 250 μL of water. The penetration d
5-mm Kromasil Cyano column (KR60-5CN; 25064.6 mm), AkzoNobel
of the delivery system through the skin could be
tracked by changes in peak height position by Formula 1. Base Gel
following the 1,437 cm-1 band assigned to a CH3,
CH2 deformation. Petrolatum
Collagen and γ-PGA content in epidermis: Petrolatum (and) Decyl Oleate (and) Dicocoyl Pentaerythrityl
Distearyl Citrate (and) Sorbitane Sesquioleate (and)
The epidermal delivery of collagen and γ-PGA
Cera Microcristallina (and) Paraffinum Liquidum
into reconstructed human skinb was also mea-
(and) Cera Alba (and) Aluminum Stearates
sured using Franz diffusion cells, as previously
(Dehymuls K, BASF)
described.10 The same base gel (see Formula 1)
Lanolin
including the microcapsules was introduced Piroctone Olamine (and) Phenoxyethanol (and) Benzoic Acid
into the donor chambers on the skin membrane (Nipaguard POB, Clariant)
and overlaid with water as an activator. As a

Untitled-1 1 4/1/15 11:35 AM
Testing | C&T
The flow rate was 1.2 mL/
min and the UV detector Figure 1. Epidermal delivery of toluidine blue by microcapsule
was set at a wavelength system (scale bar = 100 µm); black arrows show penetrating
of 210 nm. The injection microcapsules (a); skin was tape-stripped to remove the SC, and then
volume was 40 µL and photographed (b)
scopolamine retention
time was 7.5 min. Data was
expressed as the cumulative
γ-PGA/collagen perme-
ation/cm2 of skin surface.
Results
Epidermal delivery
of dye: The microcapsule
content is made of col-
lagen and γ-PGA. Upon
topical activation, the
content of these organelles
is ejected through the Figure 2. Raman spectra of microcapsule gel on glass substrate
collagenous shaft into the before and after water activation
upper skin layers (i.e.,
upper epidermis). Figure 1
demonstrates the ex vivo
delivery of hydrophilic
toluidine blue dye, serving
as an internal marker for
the microcapsule γ-PGA
Absorbance (A.U.)
content on full thickness

porcine skin. As can be
seen, the dye was delivered
beneath the skin
barrier to the upper
epidermis.
Microcapsule penetra-
tion depth: Figure 2 shows
the Raman spectra of the
delivery system before and
5 min after the addition
of water. The changes
in the Raman spectra Figure 3. Three separate experiments show penetration depth of
reflect the conformational the microcapsule needles after activation with water
changes that occur to the
γ-PGA/collagen structural
components following
activation. The fact that
there are differences is not
inconsistent with properties
of the mechanism, given
that collagen is not a part
of the capsule after activa-
tion. Penetration of the
delivery system through
the skin could be tracked
by following the 1,437 cm-1
band assigned to a CH3,

CH2 deformation. Figure 3
shows that the delivery Figure 4. Epidermal collagen and PGA content in epidermis
system alone penetrated to following seven days of application
depths between 20 μm and
30 μm.
Collagen and γ-PGA
content in epidermis: The
amount of γ-PGA and
collagen released from the
microcapsules into the
epidermis against time
are presented in Figure 4;
note that mammalian and
marine collagen content
could be differentiated.
Data are expressed as the
cumulative γ-PGA/collagen
permeation per square
centimeter (cm2) of skin
surface.
Discussion and the SC layer of various skin types, i.e., human, pig
Conclusions and reconstructed human skin. In addition, the
The data presented here shows that a natural system delivered substantially higher amounts of
microinjection system based on the stinging cells of marine collagen and γ-PGA into tissues compared
the Cnidaria sea anemone could effectively puncture to the negligible amounts delivered by the control.

Testing | C&T
Extrapolated from the results of one week of treat- 6. AO Barrel, M Paye and HI Maibach, eds, Handbook of Cosmetic
Science and Technology, Second Edition, Taylor & Francis, Boca
ment, one month of treatment using the system could Raton, FL USA (2006)
deliver the same amount of collagen and γ-PGA as 7. L Rittié, S Kang, JJ Voorhees and GJ Fisher, Induction of
one collagen injection session.11 collagen by estradiol: Difference between sun-protected and
photodamaged human skin in vivo, Arch Dermatol 144(9) 1129-
The transepidermal delivery system described 1140 (2008)
could succeed current anti-aging interventions based 8. S Kwon Kim, Marine Cosmeceuticals: Trends and Prospects,
on partial solutions and/or highly invasive methods CRC Press (2011)
to effectively and safely deliver key substances such as 9. Y Kitagawa, S Shirahata and K Teruya, eds, Animal Cell Technol-
ogy: Basic & Applied Aspects, Springer, Heidelberg, Germany
collagen. It also can replace higher-risk or less desired
(2004)
mammalian ingredients with uniquely advantageous 10. J Ahn, E Lee, J Lee, N Kim and Y Oh, The anti-aging effects of
marine collagen and γ-PGA. This delivery system poly-gamma-glutamic acid on broad band ultraviolet B light–
therefore fills an unmet need that has, up to now, induced photoaging skin in a mice model, J Amer Acad Derm
64 (2 suppl 1) AB20 (2011)
appeared to have been unattainable.
11. MH Gold, Use of hyaluronic acid fillers for the treatment of the
aging face, Clin Interv Aging 2(3) 369–376 (2007)
References
1. K Se-Kwon, Seafood Processing By-products Trends and
Applications, Springer, Heidelberg, Germany (2014)
Additional Reading
2. A Ogunleye, A Bhat, VU Irorere, D Hill, C Williams and R Tal, A Ayalon, A Sharaev, Z Kazir, V Brekham and T Lotan,
I Radecka, Poly-γ-glutamic acid—Production, properties and Continuous drug release by sea anemone Nematostella vecten-
applications, Microbiology (in press) sis stinging microcapsules, Marine Drugs 12 734-745 (2014)
3. MH Sung, C Park, CJ Kim, H Poo, K Soda and M Ashiuchi, R Paleco, SR Vuĉen, AM Crea, A Moore and S Scalia, Enhance-
Natural and edible biopolymer poly-gamma-glutamic acid: ment of the in vitro penetration of quercetin through pig skin by
Synthesis, production and applications, Chem Rec 5(6) 352-366 combined microneedles and lipid microparticles, Int J Pharm
(2005) 472 206-213 (2014)
4. N Ben-Zur and DM Goidman, γ-Polyglutamic acid: A novel

peptide for skin care, Cosm & Toil 122(4) 64-72 (2007)
5. MB Brown, BP Martin, SA Jones and FK Akomeah, Dermal
and transdermal drug delivery systems: Current and future
prospects, Drug Delivery 13 175-187 (2006)

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Untitled-3 1 4/1/15 11:57 AM

Formulating | C&T
Bakuchiol to Stabilize
Retinol and
Ratan K. Chaudhuri, PhD
Sytheon Ltd., Boonton, NJ USA
Boxin Ou, PhD
International Chemistry Testing, Milford, MA USA
S
tructurally, bakuchiol (see Figure 1) belongs to the family of
KEY WORDS meroterpenes, which are terpenes having an aromatic ring in their
structure. Bakuchiol possesses antioxidant,1-4 anti-inflammatory,5-8
retinol • bakuchiol • anti-bacterial,9 anti-tumor,10, 11 hepatoprotective12 and caspase-3-dependent
linoleic acid • squalene • apoptosis13 properties. It has been shown to inhibit melanin produc-
xymenynic acid • tion tenfold over arbutin, in a dose-dependent manner without strong
antioxidant • stablization • cytotoxicity.14
lipid peroxidation • Furthermore, bakuchiol protects mitochondria against oxidative stress,3
photo-oxidation maintains mitochondria membrane structure integrity,15 and has been
shown to protect against mitochondria genome damage.16, 17 Bakuchiol’s
topical application has recently been reviewed by Chaudhuri.18 Although
bakuchiol has been known since 1973, and has shown physiological
ABSTRACT
properties beyond those described,4, 18-21 its first commercial use in topical
Bakuchiol, a meroterpene applications did
of plant origin, is examined not occur until
here for its ability to stabilize 2007.22 Here, the
Figure 1. Structure of bakuchiol
retinol and polyunsaturated authors investi-
lipids. It was found to gate its ability to
stabilize retinol
be approximately 60-
and polyun-
fold more effective than saturated lipids,
natural tocopherol, under which are key
both photo-oxidative ingredients for
and singlet oxygen skin care.
environments. An overview
of retinol stabilization, lipid Retinol
Figure 2. Structure of retinol
peroxidation and the unique Properties
role lipid peroxides play in Retinol or
biology also is included. vitamin A (see
Figure 2) has
been around for
well over eighty
Save to years. It was
My Library studied by Paul
Karrer, a Swiss

CT1505_Formulating_Chaudhuri_fcx.indd 64 4/13/15 1:43 PM

SUNPROTECTION: 9-10 JUNE 2015
Royal College of Surgeons,
CONFERENCE 2015
INSPIRATIONS FROM NATURE
London, UK
13th in the series of
biennial international
Sun Protection
Conferences
Can Nature help us to develop future sun protection strategies?
The first sunscreens protected against sun burning and were essentially
UVB protectants with low factors that allowed easy tanning of the skin.
Modern sunscreen products may still provide highly heterogeneous attenuation Are there other wavelengths that we should consider in our protection
of the sun’s rays not necessarily consistent with the quality of electromagnetic strategies? What does natural protection tell us about the biological need?
radiation experienced in Nature.
Following the theme of the conference this year, we will explore and re-examine
As an industry we have been driven by the quantity of protection as indicated by sun product development strategies in terms of quality of protection, natural
the SPF and not necessarily the quality of protection. A level of UVA protection substances and human behaviour. In addition, internationally renowned expert
is now a requirement for most markets worldwide, but is this sufficient in speakers have been invited to give an update on sun care technology, testing
terms of quality and quantity of broadspectrum protection? and worldwide regulations affecting the development, testing, and promotion
of sun products.
Tuesday 9 June 2015

Session 1 - Can Nature direct our sun protection strategies? Session 2 - Old and new sun protection issues
Chairman’s opening - Dr Jack Ferguson, Skinnovation Ltd, UK Session 2 Chairman - John Staton, Dermatest Pty Ltd, Australia
Paper 1 - Keynote - Spectral homeostasis – a property of future sunscreens? Paper 6 - Is photoprotection necessary for ethnic skin types?
Uli Osterwalder, BASF, Germany Dr J Nash, The Procter & Gamble Company, USA
Paper - Spectral variations of solar UV due to natural and built factors Paper 7 - Ocular protection from UV radiation and the derivation of a Sun
Professor Alfio Parisi, Faculty of Health, Engineering and Sciences, University of Protection, Factor equivalent for UV-blocking contact lenses
Southern Queensland, Australia Anna Sulley, Johnson & Johnson Vision Care EMEA
Paper 3 - A global approach to sun protection - UV, visible, IR Paper 8 - Suntanning with sunscreens: a comparison with sunbed tanning
Dr Marc Pissavini, Coty Lancaster, Monaco Uli Osterwalder, BASF, Germany
Paper 4 - Natural photoprotection afforded by the human body: Paper 9 - Keynote - US sunscreen regulation and the OTC drug review
the contributions of melanin, hair and shadow Jennifer Rempe, Energizer Personal Care, USA
Professor Paul Matts, Procter & Gamble HABC Ltd, UK Discussion - Current topics will be discussed by panel and audience
Paper 5 - Keynote Sunshine protection: what are we trying to achieve? Wine & canapés reception - Open to all participants
Dr Richard Weller, University Department of Dermatology, Edinburgh, UK
Wednesday 10 June 2015

Session 3 - Consumer trends, regulatory issues and in vitro Session 4 - Sun protection technologies
measurement of sun protection
Chairman’s opening - Dr J Nash, The Procter & Gamble Company, USA Session 4 Chairman - Dr Jack Ferguson
Paper 10 - Sun protection - Consumer trends and product innovations Paper 14 - Revisiting human skin, sunscreen films and protection performance.
Ramaa Chipalkatti, Datamonitor Consumer, UK Can we create the ideal high performance sunscreen?
Paper 11 - Sun product regulations: global update Dr Jürgen Vollhardt, DSM Nutritional Products Ltd, Switzerland
Debra Redbourn, dR Cosmetic Regulations, UK Paper 15 - In silico, in vitro and ex vivo studies identified strong UV-
Paper 12 - In vitro SPF for label claim: fact or fiction protective effects of a phytocompound
Dr Dominique Lutz, HelioScreen Cosmetic Science, France Dr Christina Österlund, Oriflame Cosmetics AB, Sweden
Paper 13 - DGK Ring-Test: In vitro UVA-Protection of Sunscreens – A Keynote address - Natural or efficient - does nature compromise science?
Comparison of ISO 24443 and FDA Final Rules 2011-14766 John Staton, Dermatest Pty Ltd, Australia
Mathias Rohr Concluding remarks and discussion
Who should attend? This will be an important meeting for all professionals interested in sun protection, including R&D managers and directors,
dermatologists, marketing and product managers, retailers of sun care products, regulatory affairs personnel, formulation chemists, product valuation
scientists, research scientists, raw materials suppliers and suppliers of sun product testing apparatus.
For booking information go to www.summit-events.com

Or contact Summit Events Ltd, Lead sponsors:
20 Grosvenor Place, London, SW1X 7HN
Tel: +44 (0)20 7828 2278

Email: info@summit-events.com
Untitled-1 1 4/13/15 10:23 AM

Formulating | C&T
chemist who was awarded a Nobel Prize in Chem- to be more photochemically labile than retinol.29 The
istry in 1937 for related investigations of vitamins A biological effects caused by photoexcitation of RP
and B2, carotenoids and flavins. When applied to are not well-understood, but studies have shown that
human skin, retinol penetrates and is sequentially photo-irradiated RP is phototoxic and photoclasto-
oxidized to retinal, then retinoic acid, subsequently genic.30 Many attempts have been made to improve
causing retinoic acid-like effects.23 Tight regulation the stability of retinol with limited success. A few,
of retinoic acid activity in the skin is imperative for selected from the literature, are as follows.
maintaining epithelial homeostasis. Compared to
retinoic acid, retinol is more stable and induces less Stabilizing Retinol: Attempts
skin irritation.24, 25 It also provides anti-aging effects Tesoriere et al. showed a synergistic interac-
and is therefore the preferred skin care ingredient tion between retinol and tocopherol against lipid
peroxidation in phosphatidylcholine liposomes.31
Peroxidation was evaluated using malondialdehyde
The relative production as an indicator of antioxidant activity; the
data suggested that by limiting the auto-oxidation
susceptibilities of lipids of retinol, alpha-tocopherol strongly promoted its
antioxidant effectiveness.
to oxidation depend on Young and Gregoriadis reported that retinol in
liposomes with tocopherol and oxybenzone exhibited
the reaction milieu a marginal improvement in stability.32 Lee et al.
incorporated retinol into multilamellar liposomes
as well as their prepared from soybean phosphatidylcholine,33 as
inherent structure. well as into liposomes containing soybean phospha-
tidylcholine and cholesterol at various ratios. Retinol
stability was enhanced by increasing the cholesterol
content; further, results indicated that cholesterol in
over retinoic acid. However, retinol is not without the liposomes increased the incorporation efficiency
flaws, and its widespread use, even with newer ana- of retinol.34
logs, is still restricted due to undesirable side effects Jee et al. reported on the stabilization of all-trans
such as irritation, dryness, peeling, erythema and retinol (AR) by loading lipophilic antioxidants in
a burning sensation on the skin.26, 27 Under certain solid lipid nanoparticles (SLNs).35 This decelerated
circumstances, retinol treatments can also cause free the degradation of AR, as compared with an AR
radical generation and induce oxidative stress. Mei solution dissolved in methanol; at 12 hr, the pho-
et al., for example, have shown in mouse lymphoma tostability of AR in SLNs was reported to be ~43%,
cells that retinol is mutagenic when exposed to UVA whereas in methanol solution, it was only ~11%. In
through a clastogenic mode of action.28 a different approach, Sapino et al. used two synthetic
In addition, retinol esters such as retinyl palmitate alkylcarbonates of γ-cyclodextrins to improve the
(RP) are commonly used in skin care, and although stability and water-solubility of retinol.36 These inclu-
these storage forms of retinol are required in many sion complexes increased the stability of retinol to
essential biological processes, they have been shown both light and heat.
A pilot study was conducted by Akhavan and Lev-
itt to assess retinol stability in a hydroquinone (4%)
Market Intelligence and retinol (0.3%) cream, in the presence of antioxi-
dants and sunscreen. Results indicated approximately
n According to a report by Canadean, Italian 10% degradation of retinol in 4 hr under simulated
consumers desire makeup to cover age-related use conditions, including exposure to UV light,
skin impurities. In fact, 19.4% of makeup oxygen and body temperature.37 Similarly, Bonda and
consumption in Italy is driven by anti-aging needs. Zhang showed an increase in retinol photostability
“Older generations will also pay greater attention when combined with ethylhexyl methoxycrylene,38
to the ingredients they already know, such as although improving the stabilization of 0.1% retinol
collagen and retinol that protect skin from aging required inefficient levels of 4% to 5% ethylhexyl
processes,” added Veronika Zhupanova, analyst at methoxycrylenea.
Canadean. Cho et al. described enhanced skin permeation
and UV/thermal stabilization of retinol emulsions by
Source: GCI (GCImagazine.com)
a
Solastay, Hallstar

using polysorbate-20 and biodegradable poly(ethylene
oxide)-block-poly(ε-caprolactone)-block-poly(ethylene
oxide) (PEO-PCL-PEO) triblock copolymers having a lon-
ger hydrophobic PCL block length. The results suggested
that HLB and PCL block length are important factors to
enhance the topical delivery of retinol into skin.39
One commercially available retinol stabilized with
BHT and BHA is reported to remain stable for 24 months
when stored at 20°C in its original sealed containers;
however, it rapidly degrades when stored at 40°C. Another
blend of retinol (42.75% to 49.50%), diluted in polysor-
bate 20 and stabilized with BHT and BHAd, has a similar
stability profile.
Linoleic acid (LA) (see Figure 3) is an unsaturated
omega-6 fatty acid that is a colorless liquid at room tem-
perature. Chemically, linoleic acid is an 18-carbon chain
carboxylic acid with two cis double bonds; the first double
bond is located at the sixth carbon, and the second is at
the ninth carbon from the methyl end.40 LA is an essential
fatty acid that the body cannot synthesize.
LA has been used in cosmetics and personal care prod-
ucts for its beneficial effects on skin. Research points to its
anti-inflammatory, acne-reductive and moisture-retentive
properties when applied topically on the skin.41-43 Also,
the lack of LA causes hyperkeratinization, barrier func-
tion disruption and bacterial proliferation.44 LA has been
reported to lighten UV-induced skin pigmentation45 due
to the post-translational degradation of tyrosinase,46 and to
improve robustness of cells.47 One study was published on
the effects of a combination of LA and vitamin C on more
than 30,000 individuals, in which marked improvements
in senile dryness (as a result of aging) and skin atrophy
(thinness) were observed.48
A simple ester of LA, ethyl linoleatee (EL), is a more
stable form of LA that is soluble in a wide range of solvents
Figure 3. Structure of LA
Suppliers Referenced
Tween 20 (INCI: Polysorbate-20), Croda,
www.croda.com/pc
Retinol 50 C (INCI: Retinol (and) Polysorbate-20), BASF,

www.personal-care.basf.com
d
Retinol GS50, DSM Nutritional Products
e
Synovea EL, Sytheon Ltd.

Formulating | C&T
and emollients. EL is hydrolyzed to LA in vivo,49 the osmotic pressure and leading to swelling, eventu-
thereby providing all the skin benefits of LA. EL is ally causing cell death.56 The chemistry involved
reported to accelerate wound healing and has been in initiating and propagating lipid peroxidation is
clinically proven an effective anti-acne agent.50 summarized in Figure 6.
Squalene (see Figure 4) is a natural 30-carbon The propensity of polyunsaturated lipids to form
polyunsaturated lipid and an omega-2 oil. As a lipid peroxides has attracted research attention in
hydrocarbon and triterpene, it is a natural and vital recent decades. One reason is due to the unique role
part of the synthesis of all plant and animal sterols, that lipid-derived peroxides play in biology, both
including cholesterol, steroid hormones and vitamin as modulators of enzymes and as intermediates
D in the human body. It is a natural moisturizer; in biosynthetic processes.57 The primary products
however, it is highly susceptible to aerial oxidation. of autoxidation are peroxides or hydroperoxides,
Therefore squalane, which is a saturated form of but these compounds are frequently unstable and
squalene, is commonly used in personal care. The decompose to aldehydes, ketones and other reac-
biological importance and applications of squalene tive substances. A great diversity of aldehydes is
and squalane were recently published by Kim and formed when lipid hydroperoxides break down.
Karadeniz.51 Some of these aldehydes are highly reactive and may
Ximenynic acid (XA) (see Figure 5) is typically be considered as second toxic messengers, which
extracted from Santalum album (sandalwood tree). It disseminate and augment initial free radical events.
is a yellow crystalline powder, which, due to the pres- The aldehydes studied most intensively thus far are
ence of a triple and double bond in the structure,
is highly susceptible to aerial oxidation. Regard- Figure 4. Structure of squalene
ing XA, limited information is publicly available.
This ingredient is supplied by two major manu-
facturers and one version claims to be stabilized
using tocopherol. Traditionally, the Santalum
album plant is used in ayurvedic treatments to
make skin smoother and tauter.
Free fatty acids and squalene comprise sebum.
Squalene is one of the most common lipids Figure 5. Structure of XA
produced by human skin cells,52 which as noted,
is highly susceptible to peroxidation and pho-
todegradation. By-products of these processes
include squalene peroxides, which promote
acne, roughening of the skin and wrinkling.53, 54
Polyunsaturated free fatty acids degen-
erate and promote the peroxidation Figure 6. Initiation and propagation of lipid peroxidation
of nearby lipids, including squalene.
Specific aspects of these processes are
described next.
Lipid Peroxidation
While the mechanisms and
sequence of events by which free
radicals interfere with cellular
functions are not fully understood,
one of the most important oxidative
events seems to be lipid peroxida-
tion, which results in cell membrane
damage. Lipid peroxidation refers to
the oxidative degradation of lipids. It
is the process by which free radicals
“steal” electrons from the lipids in cell
membranes, thereby resulting in cell
damage.55 This damage causes a shift
in the net charge of the cell, changing

4-hydroxynonenal (4-HNE), 4-hydroxyhexanal and malondialdehyde.58
Both medium-chain aldehydes, obtained from polyunsaturated lipid oxida-
tion, and retinoids exert potent biological activities. For example, 4-HNE reacts
spontaneously with glutathione and with cysteine, histidine, and lysine residues
in cellular proteins, causing a variety of cytotoxic and genotoxic effects.59 High
levels of all-trans-retinaldehyde are also cytotoxic. The finding that 4-HNE
strongly inhibits the biosynthesis of retinyl esters and retinoic acid suggests that
oxidative stress and lipid peroxidation can have deleterious consequences for the
overall retinoid homeostasis in cells. Also, Xia et al. showed that retinyl palmitate
acts as a photosensitizer, leading to the formation and induction of lipid peroxi-
dation following irradiation with both UVA and UVB light.60 Recently, Aldini et
al. have shown detrimental effects of UVB radiation on 4-HNE metabolism and
toxicity in human keratinocytes.61
Materials and Methods

Considering the propensity of polyunsaturated lipids to form lipid peroxides,
and the instability issues and storage restrictions of retinol, the present authors
sought to determine whether bakuchiol, which has broad-spectrum antioxidant
properties, could stabilize retinol and other polyunsaturated lipids including LA,
squalene and XA. The study also assessed the capability for bakuchiol to stabilize
under photo-oxidative and singlet oxygen environments.
Retinolc was purchased commercially for the present study. This particular
yellow oil forms crystals at low temperatures, is soluble in polysorbate 20, has an
assay of approximately 50%, and is included a stabilizer system of ~3.5% BHT
and ~1% BHA. Bakuchiolf having a minimum of 95% purity, as determined by
quantitative HPLC analysis, was procured from the author’s company. The LAg
and squaleneh purchased for this study had purities of ≥ 99% and ≥ 98%, respec-
tively. The XA usedj had a purity of ≥ 98%.
Stabilizing lipids under peroxidation: Lipid peroxidation was initiated by
adding 100 µL of 100 mM 2,2’-azobis (2,4-dimethylvaleronitrile or AMVN), a
lipophilic-free radical initiator, to the retinol or lipid substrates and bakuchiol
at different concentrations. The mixtures were then incubated at 37°C over-
night. Decomposition of the unstable peroxides resulted in the formation of
malondialdehyde (MDA), which was quantified colorimetrically at 532 nm.
MDA is a well-known index of lipid peroxidation; this protocol is detailed by
Botsoglou et al.62
Stabilizing retinol under photo-oxidation: Retinol (50 µg/mL) was dis-
solved in ethanol in 5-mL vials, to which bakuchiol was added at different
concentrations: 50 µg/mL, 100 µg/mL and 200 µg/mL. Test vials were placed in a
photochemical reactor equipped with UVA and UVB lampsk, to simulate daylight
conditions. The samples were irradiated at 31°C for 5 min at a dose of 13 J/cm2.
Retinol was quantified by HPLC. The mobile phase consisted of 75% A (acetoni-
trile) and 25% B (methanol), isocratically run at 1 mL/min for 10 min.
Stabilizing retinol under singlet oxygen (1O2): Retinol (50 µg/mL) was
dissolved in ethanol in 5 mL vials, then bakuchiol was added at different concen-
trations: 50 µg/mL, 100 µg/mL and 200 µg/mL. Singlet oxygen was generated
by the addition of H2O2 and lithium molybdate, resulting in a mixture with a
pH of around 9. This mixture was then incubated at 37°C in the dark for 15
hr. During this period, singlet oxygen was generated and retinol was oxidized.
Retinol was then quantified by HPLCm. Again, the mobile phase consisted of
f
Sytenol A (INCI: Bakuchiol), U.S. Patents 8,529,967 and 8,859,0210; and pending U.S. and international
patents; Sytheon Ltd.
g, h
Sigma-Aldrich, St. Louis, MO
j
Shanghai Tauto Biotech Ltd.
k
Rayonet RPR-100, Southern New England Ultraviolet Company
m
Luna C 18, 4.6 × 250 mm column, equipped with DAD detector at 280 nm, Phenomenex, Torrance

Formulating | C&T
75% A (acetonitrile) and 25% B (methanol), isocrati- their inherent structure. The oxidation of linoleates
cally run at 1 mL/min; this protocol is described in has been discussed in some detail by Niki et al.64 The
Tetrahedron Letters.63 peroxidation of squalene in its unsaturated form
in sebum reportedly occurs more easily than the
Results and Discussion peroxidation of palmitoleic or oleic acid.65 Squalene
Lipids under peroxidation: Results demonstrated peroxidation occurs gradually by UV irradiation,
that bakuchiol significantly protected lipids from with an increase in the formation of squalene perox-
peroxidation (see
Figure 7). It was a
potent inhibitor of
Figure 7. Inhibition of lipid peroxidation by bakuchiol (in μg/mL)
lipid peroxidation,
with IC50 and IC100
ranging from 0.5 to
0.8 and 1.4 to 2.3 µg/
mL, respectively.
Comparing IC50 val-
ues, bakuchiol was
also 50- to 60-fold
more effective than
natural tocopherol.
Note that the
relative suscepti-
bilities of lipids to
oxidation depend
on the reaction
milieu as well as

ide, which has been reported to form even after small Retinol under photo-oxidation: A characteristic
suberythematogenic doses of UVA (5 J/cm2).66 feature of retinoids is their instability to UV light.
Recently, Ryu et al. showed that the topical appli- UVA (320 nm to 400 nm) and UVB (290 nm to
cation of squalene peroxide in guinea pigs induces 320 nm) have been shown to reduce retinol content
skin hyperpigmentation by increasing the release of in human skin.71 Pathways for photodegradation of
prostaglandin E2 (PGE2) from keratinocytes.67 Squa- retinoids include photoisomerization, photodimer-
lene peroxide was also associated with the initiation ization and photo-oxidation.72 Sunlight-induced
of the inflammatory cascade, triggering cytokines photodegradation of retinyl esters proceeds much
and the lipoxygenase pathway. Furthermore, it is faster than that of retinol, and it has been suggested
also present in acne;68 therefore, it is expected that that Cellular Retinol Binding Protein-1 (CRBP-1)
bakuchiol could stabilize squalene and thereby may protect retinol from photodegradation. How-
protect skin from photo-induced damage, providing ever, studies using hairless mice treated topically with
a reduction in hyperpigmentation and reducing the retinol before and after UVB exposure showed that
severity of acne. retinol was depleted to a similar extent after UVB
A separate study of stabilized, 0.1% retinol-con- exposure of the pretreated animals as compared to
taining moisturizer was carried out in comparison untreated animals in spite of an induction CRBP-1.
with its vehicle in women having moderate facial Sorg et al.73 have suggested that UV light depletes
photodamage. Results showed that, after eight weeks, epidermal retinol through a photochemical reac-
the retinol moisturizer was significantly more effica- tion rather than via oxidative stress. Generation of
cious than the vehicle in improving lines, wrinkles, reactive oxygen species accompanying irradiation of
pigmentation, elasticity,
firmness and overall
photodamage.69 Bakuchiol Figure 8. Percent improvement of retinol (R) stabilization under
has also been demon- photooxidative environment with bakuchiol (B)
strated clinically to have
broad-spectrum anti-aging
activity;18 it would be inter-
esting to evaluate whether a
bakuchiol-stabilized retinol
containing product would
provide improvements,
potentially synergistically,
in the appearance of aged
and/or photo-aged skin.
Rate constants for reac-
tions of all-trans retinol and
retinal with singlet oxygen
were measured by Smith
in a variety of solvents
having different polarities.70
The constants were found
Figure 9. Percent improvement of retinol (R) stabilization under
to increase with increasing
singlet oxygen environment with bakuchiol (B)
solvent dielectric constant,
which suggests a charge
transfer mechanism is play-
ing a part in the reaction.
Further, the rate constant
reaction of singlet oxygen
with retinal was greater
than with retinol, and since
retinal has a lower ioniza-
tion potential than retinol,
these relative rates also
support the hypothesis of
charge transfer involvement
in the reaction.

Formulating | C&T
retinol, retinyl palmitate, and their corresponding photo-
decomposition products has been demonstrated by several
authors.74, 75 Membrane damage induced by the attack
of singlet oxygen on the lipid or protein moieties can be
highly deleterious.
Results demonstrated that bakuchiol dose-dependently
protected retinol in vitro from photo-degradation.
Figure 8 summarizes the results obtained from this study.
Use of 1:1 and 1:2 (w/w) showed moderate improvement
in the stability of retinol 30% (46% to 60%) and 56% (46%
to 72%), respectively, with bakuchiol. However, a four-fold
increase in bakuchiol provided complete stabilization
of retinol. It would be interesting to evaluate whether
bakuchiol-treated skin could stabilize epidermal retinol
under a photo-oxidative environment.
Retinol under singlet oxygen: Singlet oxygen is an
oxygen molecule that has been excited from its ground
triplet state to its first singlet state. After excitation, singlet
oxygen decays within microseconds, which is due to inter-
action with molecules in its environment. Photochemical
studies have demonstrated that excitation of retinol or its
esters with UV light generates a number of reactive species
including singlet oxygen and superoxide radical anion.76
Singlet oxygen reacts with olefinic double bonds to pro-
duce hydroperoxides by a concerted ene-type mechanism.
These reactive oxygen species have been shown to damage
a number of cellular targets, including lipids and DNA.
Consistent with the potential for damaging DNA, retinyl
palmitate has been shown to be photomutagenic in an in
vitro test system.
These results demonstrated that under a singlet oxygen
environment, bakuchiol dose-dependently protected
retinol in vitro from photo-degradation. Figure 9 sum-
marizes the results obtained from this study. Use of only
two-fold excess of bakuchiol provided complete stabiliza-
tion of retinol.
Conclusion
Bakuchiol, a meroterpene of plant origin, shows
promise as a new agent that can complement and enhance
the effectiveness of retinol and a range of polyunsatu-
rated lipids, including squalene, LA and XA, due to the
improved stability it imparts in different oxidative environ-
ments. Bakuchiol also has a wide range of beneficial skin
properties, and its excellent safety profile, and photo- and
hydrolytic-stability are advantages over retinol; thus,
bakuchiol can be used throughout the day.18 Topical for-
mulations that include bakuchiol are likely to lead further
improvements in the way aged or problem skin are treated
now and in the future.
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tagenicity of retinyl palmitate by ultraviolet A irradiation in mouse trial Chemistry, Wiley-VCH, Weinheim, Germany (2006)
lymphoma cells, Toxicolog Sci 88 142-149 (2005) 41. WE Diezel, E Schulz, M Skanks and H Heise, Plant oils: Topical
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and MA Livrea, Synergistic interactions between vitamin A tologische Monatsschrift 173(179) (1993)
and vitamin E against lipid peroxidation in phosphatidylcholine 42. C Letawe, M Boone and GE Pierard, Digital image analysis of
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and its protection with tocopherol and oxybenzone, Photochem 43. GL Darmstadt et al, Impact of topical oils on the skin barrier:
Photobiol 63(3) 344-352 (1996) Possible implications for neonatal health in developing countries,
33. SC Lee, HG Yuk, DH Lee, KE Lee, YI Hwang and RD Ludescher, Acta Paediatrica 91(5) 546–554 (2002)
Stabilization of retinol through incorporation into liposomes, 44. DT Downing, ME Stewart, PW Wertz and JS Strauss, Essential
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34. SC Lee, KE Lee, JJ Kim and SH Lim, The effect of cholesterol in 45. H Ando, A Ryu, A Hashimoto, M Oka and M Ichihasi, Linoleic
the liposome bilayer on the stabilization of incorporated retinol, acid and alpha-linolenic acid lightens ultraviolet-induced hyper-
J Liposome Res 15(3-4) 157-166 (2005) pigmentation of the skin, Arch Derm Res 290 375-381 (1998)
35. JP Jee, SJ Lim, JS Park JS and CK Kim, Stabilization of all-trans 46. H Ando et al, Fatty acid regulate pigmentation via proteosomal
retinol by loading lipophilic antioxidants in solid lipid nanopar- degradation of tyrosinase: A new aspect of ubiquitin-proteos-
ticles, Eur J Pharm Biopharm 63(2) 134-139 (2006) ome function, Biochem J 394 43-50 (2004)
36. S Sapino, ME Carlotti, R Cavalli, M Trota, F Trotta and D Vione, 47. M Butler, N Huzel, N Barnabé, T Gray and L Bajno, Linoleic acid
Effect of akyl-c-cyclodextrins on the stability of retinol, J Incl improves the robustness of cells in agitated cultures, Cytotech-
Phenom Macrocycl Chem 57 451–455 (2007) nology 30(1-3) 27-36 (1999)
48. MC Cosgrove, OH Franco, SP Granger, PG Murray and
AE Mayes, Dietary nutrient intakes and skin-aging appearance
among middle-aged American women, Am J Clin Nutr 86(4)
1225-1231 (2007)
49. BL Hungund, Z Zheng and AI Barkai, Turnover of ethyl-linoleate
in rat plasma and its distribution in various organs, Alcohol Clin
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50. A Charakida, M Charakida and AC Chu, Double-blind, random-
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citrate and ethyl linoleate in the treatment of Acne vulgaris, Brit
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51. SK Kim and F Karadeniz, Biological importance and applica-
tions of squalene and squalane, Adv Food Nutr Res 65 223-233
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52. M Spanova and G Daum, Squalene—Biochemistry, molecular
biology, process biotechnology and applications, Eur J Lipid Sci
Technolo DOI: 10.1002/ejlt.01100203 (2011)
53. K Chiba, K Yoshizawa, I Makino, K Kawakami and M Onoue,
Comedogenicity of squalene monohydroperoxide in the skin
after topical application, J Toxicological Sciences 25 77–83
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54. K Chiba, T Sone, K Kawakami and M Onoue, Skin rough-
ness and wrinkle formation induced by repeated application
of squalene-monohydroperoxide to the hairless mouse, Exper
Dermatol 8 471–9 (1999)
55. B Halliwell and S Chirico, Lipid peroxidation: Its mechanism,
measurement and significance, Am J Clin Nutr 57(5) 715S-724S
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K van Norren and PA van Leeuwen, Flavonoids: A review of
probable mechanisms of action and potential applications,
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57. DA Pratt, KA Tallman and NA Porter, Free radical oxidation of
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opment of peroxyl radical clocks, Acc Chem Res 44(6) 458–467
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58. H Esterbauer, RJ Schaur and H Zollner, Chemistry and biochemistry of
4-hydroxynonenal, malonaldehyde and related aldehydes, Free Radical
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59. H Esterbauer, Cytotoxicity and genotoxicity of lipid-oxidation products,
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species and lipid peroxides, Int J Envron Res Public Health 3(2) 185-190
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61. G Aldini, P Granata, C Marinello, G Beretta, M Carini and RM Facino,
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and toxicity in human keratinocytes, Chem Res Toxicol 20 (3) 416–423
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62. NA Botsoglou, DJ Fletouris, GE Papageorgiou, VN Vassilopoules,
AJ Mantis and AG Trakatellis, Rapid, sensitive and specific thiobarbitu-
ric acid method for measuring lipid peroxidation in animal tissue, food
and feedstuff samples, J Agric Food Chem 42 1931-1937 (1994)
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tion from H2O22/MoO 4 2-: Peroxidation of hydrophobic substrates in
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64. E Niki, Y Yoshida, Y Saito and N Noguchi, Lipid peroxidation: Mecha-
nisms, inhibition and biological effects, Biochemical and Biophysical
Research Communications 338(1) 668-676 (2005)
65. K Ohsawa, T Watanabe, R Matsukawa, Y Yoshimura and K Imaeda,
The possible role of squalene and its peroxide of the sebum in the
occurrence of sunburn and protection from the damage caused by UV
irradiation, J Toxicol Sci 9(2) 151-159 (1984)
66. ES Mudiyanselage, M Hamburger, P Elsner and JJ Thiele, Ultraviolet a
induces generation of squalene monohydroperoxide isomers in human
sebum and skin surface lipids in vitro and in vivo, J Invest Dermatol
120(6) 915-922 (2003)
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molecule in skin hyperpigmentation caused by singlet oxygen,
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Acne vulgaris: Old wine in new bottles, Lipids Health Dis 9 141 (2010)
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Vitamin A exerts a photoprotective action in skin by absorbing ultraviolet
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76. PP Fu et al, Photodecomposition of vitamin A and photobiological
implications for the skin, Photochem Photobiol 83 409–424 (2007)

Formulating | C&T
Topical Delivery of
Vitamin D for Well-being
Celeste Hilling
Skin Authority, Carlsbad, CA USA
T
he “Vitamin D Revolution,” as proclaimed by many doctors and
KEY WORDS experts, is just beginning to uncover the significance of vitamin D
for health. In the last decade, vitamin D has gone from recognition
vitamin D • diet • primarily for its role in bone health to being investigated for possible roles
psoriasis • topical delivery • in a wide range of body functions and in the prevention of diseases—from
chemiluminescence cancer and diabetes, to multiple sclerosis and depression.
Vitamin D is the only vitamin that the body actually makes. It is made
in the skin and converted to a hormone. When vitamin D hormone levels
are balanced, auto-immune skin conditions such as eczema, psoriasis and
rosacea improve.
ABSTRACT
As a skin care formulator, this author began three years ago to research
Topical application of vitamin D. Speaking with researchers and medical specialists expanded
antioxidants and minerals her appreciation for the critical importance of enhancing vitamin D health
has become a focal inside and outside. Supporting this statement, Michael F. Holick, PhD, MD,
point among the medical wrote in his work, The Vitamin D Solution, “If I had to give you a single
community. Here, the secret ingredient that could apply to the prevention—and treatment, in
many cases—of heart disease, common cancers, stroke, infectious diseases
rationale for the topical
from influenza to tuberculosis, dementia, depression, insomnia, joint pain,
delivery of vitamin D is rheumatoid arthritis, osteoporosis, psoriasis and hypertension, it would be
described, including the this: Vitamin D.”
review of a case study There are two principle types of vitamin D: D2 and D3, as well as other
suggesting real efficacy. active analogs. Ergocalciferol (D2) is derived from sources such as forti-
This, taken in conjuction fied milk, herring, mackerel, tuna, salmon, sardines, eggs, fortified cereals
with the described results, and baked goods. Vitamin D3, otherwise known as cholecalciferol, is
led to the development photochemically produced upon UV exposure from the precursor sterol
7-dehydrocholesterol, which is present in the epidermis. Vitamin D3 is an
of a concept combining
essential nutrient and pro-hormone; it, too, is present in animal products
nutritional and topical
and fortified foods, and can be consumed from fish oil, eggs or fish. This
approaches to deliver article describes a pilot study researching the potential for topical vitamin
vitamin D. D3 delivery.
Vitamin D History and Deficiency

The first scientific description of a vitamin D deficiency, namely rickets,
Save to
was provided in the 17th century by both Whistler1 and Glisson. Then
My Library
in 1861, Trousseau associated rickets with a lack of sunlight exposure.
However, years passed before the work of Mellanby and McCollum in 1918,

CT1505_Formulating_Hilling_fcx.indd 76 4/13/15 2:23 PM

Untitled-3 1 4/7/15 3:01 PM
Formulating | C&T
which led to the discovery of vitamin D.1 psoriasis.4 Additionally, the use of UV light therapy in
As noted, vitamin D production begins as a conjunction with vitamin D creams has been found
chemical reaction in the skin upon exposure to UV effective. Jurgen Schauber, MD, of Ludwig-Maximil-
light—specifically UVB. With age, skin loses its lian University in Germany, explained that along with
ability to produce sufficient levels of vitamin D. The other proteins, vitamin D is a key player in activating
skin needs vitamin D to make vitamin D; therefore an inflammation-triggering inflammasome, which
depletion in the skin also limits its production. helps autoimmune skin conditions. Topical vita-
Besides aging, vitamin D deficiency can occur due to min D treatments and UVB light therapy help DNA
inadequate exposure to the sun, skin color, geography to inhibit inflammasome activation by controlling
or low levels in the diet. As the body draws on vita- cathelicidin production. In relation, Henry Lim, MD,
min D to make more, it destroys the vitamin D used chief of dermatology at the Henry Ford Hospital in
in the creation process. This cycle therefore requires Detroit, noted this study increases the understanding
more to be constantly replenished. of the role of vitamin D in psoriasis.
To reach optimal levels, it should be produced “We have used these treatments for a long time,
in the skin as well as supplied through a diet rich but we haven’t had a full understanding of why they
in vitamin D. At present, vitamin D supplements work,” Lim said, in a report by WebMD. “This is one
are available as oral and injection forms; however, potential mechanism.”5
compliance of oral vitamin D supplementation alone Recent studies also show that natural forms of
is only reported to be 20-60%.Therefore, another vitamin D—D3 in particular—can be safely delivered
reason the author was interested in supplementation by topical skin creams. This latter work inspired
of vitamin D by a topical route was to increase patient studies in Dubai to determine whether the topical
compliance. Estimates show that one billion people application of vitamin D could not only enhance the
worldwide, a figure that grows in winter months, are external skin condition, but also elevate its internal
vitamin D deficient.2 Seventy-six percent of pregnant production.
women are severely vitamin D deficient, and nearly
half (48%) of girls ages 9-11, a sizable percentage Case Study:
being minorities or individuals of darker skin, e.g., Vitamin D in the Bloodstream
Hispanic, Black and Asian, also are deficient in To test the topical delivery of vitamin D, a
vitamin D.3 It is interesting to note that in the 1980s, randomized, controlled study was conducted in 2014
the Saudi population showed low vitamin D levels; at the College of Medicine, University of Dammam,
extensive work by Sedrani et al. further revealed this King Fahd Hospital of the University, AlKhobar, in
deficiency existed not only during winter months, but Saudi Arabia.6 The purpose of the study was to deter-
also summer months due to non-exposure to the sun. mine the feasibility of topically applied vitamin D
Al-Turki et al. and Sadat-Ali et al. additionally found to transdermally enhance levels of vitamin D in the
that, in the healthy Saudi population, vitamin D bloodstream. Forty-eight healthy female medical
deficiency occurred in approximately 40-60% of men students participated in the research. Following
and women over the age of 50. medical history and clinical exams, their blood was
initially drawn for 25 Hydroxy Vitamin D3 (25OHD)
Delivery of Vitamin D3 levels, which were measured by chemiluminescence
Research suggests that supplemental vitamin D immunoassay (CLIA). In the United States, 30 mL
could block the inflammatory process of psoriasis, is threshold to describe vitamin D sufficiency; thus
and that synthetic vitamin D delivered topically > 30 mL was taken as normal, 21-29 mL as insuf-
via prescription ointments is effective in treating ficient and < 20 mL as deficient.
The participants were then divided into two
groups of 24 each. They agreed not to change their
Market Intelligence dietary habits or lifestyles, including sun exposure,
until three months later—after the study ended.
n Wellness has become a synonym of beauty. The first group applied topical vitamin D3 using an
As previously reported by Diagonal Reports, aloe vera-based cream, with each gram of the cream
consumers believe that skin appearance can be delivering 5000 IU of vitamin D3. The second group
dramatically improved by things such as reducing used 1 g of aloe vera gel without vitamin D. The
stress or increasing energy. The cosmetic is no participants had no knowledge to which group they
longer the reference point. belonged. A second blood sample was taken after
Source: GCI (GCImagazine.com) three months, and the data was analyzed.
In the control group, no statistically significant

Figure 1. 25OHD in control group, pre- and post- placebo treatment
Figure 2. 25OHD levels pre- and post-treatment with topical

vitamin D
change in 25OHD levels was observed (see Figure 1). In fact, the average was
slightly lower than the initial results at the onset of the study. In the test group,
women who had initial lower levels of 25OHD showed marked improvements.
The average 25OHD in the test group pre-treatment was 12.05 mL ± 6.54, and
post-treatment was 37.95 mL ± 6.43 (p ≤ 0.0001). In the control group (see Fig-
ure 2), the pre-treatment 25OHD was 10.4 mL ± 3.97 and post-treatment was
9.58 mL ± 3.03. The comparison between the two groups is shown in Table 1.
This study shows that vitamin D3 could effectively be delivered by dermal
route, reducing the incidence of non-compliance of oral route; furthermore, no
incidents of rashes or reactions were observed with topical treatment. While
the most common routes of administering vitamin D are oral or invasive/
injectable, the present findings suggest a third route: transdermal. For any drug,
large proportions of oral prescriptions are never taken at all.7 Recent estimates
for noncompliance range from study to study, with 62% to 84% using electronic
monitoring.8, 9 Hence, these authors believe that in the young and elderly,
the oral route can be bypassed by the use of transdermal route. Note that the

Formulating | C&T
Table 1. Comparison in 25OHD Levels Between Groups
Test Group Control Group p value

Hemoglobin level g/L 11.92 ± 0.87 11.26 ± 0.92 0.2
Calcium mg/dL 9.0 ± 0.6 8.95 ± 0.48 0.6
Phosphorus mg/dL 3.78 ± 0.66 3.7 ± 0.61 0.7
Alkaline Phosphatase U/L 74.91 ± 24.84 82.25 ± 28.19 0.01 CI < -7.148
Parathormone 8.33 ± 4.13 9.15 ± 3.74 0.2
25OHD pretreatment ng/mL 12.05 ± 6.54 11.4 ± 3.97 0.4
25OHD post-treatment ng/mL 37.95 ± 6.43 10.58 ± 3.03 0.001 CI < 28.5828
described study was funded and conducted by the become a focal point among the medical community.
University of Dubai. However, the author’s company This, taken in conjuction with the described results,
used this study data, along with other ongoing led to the development of a concept combining
studies, to develop product concepts for a topical nutritional and topical approaches to deliver ingre-
vitamin D. dients, such as vitamin D; in this case, a whole food
Since there is little research to indicate that spice powdera and topical elixir skin care lotionb was
supplements can actually make their way past the created for an inside-out approach.
acidic internal process and be deposited in skin,10
topical application of antioxidants and minerals has a
Nutritopicals and bVita D Illuminating Duo, Skin Authority

Exploring the Future
of Product Development
University of Pennsylvania Philadelphia, PA June 22–23, 2015
Two Ways to Learn Featured Topics

1) Technical Presentations
• The Material Science of
Multifunctional Cosmetics
• Environmentally Benign
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• Demystifying (and Defending)
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• Building a Robust Product Profile:
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2) Hands-on Workshops
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Formulating | C&T
Conclusions References
1. www.gpcme.co.nz/pdf/GP%20CME/Friday/C1%201425%20
Application of topical products to the skin can Harrison.pdf (Accessed Apr 1, 2015)
act locally, pass into the systemic circulation, or 2. www.ncbi.nlm.nih.gov/pubmed/18400738 (Accessed Apr 1,
2015)
do both. Although the stratum corneum (SC) is
3. www.naturalnews.com/003069.html (Accessed Apr 1, 2015)
an efficient barrier, some substances are able to
4. MK Batra and J Ropp, Improved cosmetic effect of topical
penetrate it to reach the underlying tissues and cream containing vitamin D2 and D3, San Diego, CA (Jul 2012)
blood vessels. These substances must be lipophilic, 5. Y Dombrowski, News release, Science Translational Medicine
and since vitamin D is fat-soluble, it should be able vol 3 (May 11, 2011)
to cross the skin barrier. To assist in their delivery, 6. www.ncbi.nlm.nih.gov/pmc/articles/PMC3976443/ (Accessed
Apr 1, 2015)
however, penetration enhancers may be employed.
7. J Avorn, Medications and the elderly, in J Rowe and R Besdine,
The most ideal penetration enhancer discovered to eds, Geriatric Medicine, 2nd edn, Little, Brown, Boston (1988)
date is water; hydrating the SC has been shown to 8. P Koch-Gwinner et al, Measurement of drug compliance by
increase the penetration of both hydrophilic and continuous electronic monitoring: A pilot study in elderly patients
discharged from hospital, J Amer Geriatrics Soc 40 1151–1155,
hydrophobic drugs. 11 (1942)
The present study also shows that with a daily 9. T Nikolaus et al, Elderly patients’ problems with medication.
dose of topical vitamin D, within a 90-day period, An in-hospital and follow-up study, Eur J Clin Pharmacol 49(4)
25OHD blood levels returned to a minimum normal 255–259 (1996)
10. Viruses and Diseases, Harvard Health Publications, in
level of 30 mL. In conclusion, the results of this
collaboration with MN Starnbach, Harvard Medical School
study indicate that topical vitamin D penetration is (2013)
possible, efficacious and safe for the young as well as
the elderly. Additional studies are being conducted
to establish the cosmetic benefits of topical vitamin
D to enhance skin conditions in participants who
saw elevated vitamin D levels in the bloodstream.

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Untitled-3 1 4/1/15 11:52 AM

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Cosmetics & Toiletries and governed by its editorial policy.
and full traceability. Kemin works diligently with family farm-
CT1505_SPContent_Formulating_fcx.indd 85 4/14/15 3:50 PM

Sponsored Content
Ethylhexylglycerin: Highly
Pure Quality by Patented This content is sponsored by:
Stabilization
By: schülke, Inc.
E
thylhexylglycerin is a frequently used unknown toxicological profiles can develop during storage.
multifunctional additive. Beside its deodor- Against this background, it should be considered that the
ant efficacy, it is an excellent booster of many use of impure material could provoke an increased risk of
traditional preservatives and other antimicrobial allergies not originally triggered by the main substance,
substances. It was introduced into the personal thereby potentially discrediting a valuable molecule.
care market by schülke as sensiva® SC 50; a prod-
uct with outstanding quality and comprehensive The Issue of Aging
safety data. Many organic substances undergo oxidative degradation
The stabilization of ethylhexylglycerin in (reactions). Specifically, ethers have the potential of form-
sensiva® SC 50 guarantees that the high purity is ing peroxides if exposed to air. This is also a concern for
maintained for the entire shelf–life of the material. polyethers, like ethoxylated surfactants, as has been reported
This stabilization system has been patented by in the past. Several different breakdown products can be
schülke. Unstabilized ethylhexylglycerin can form expected from primary oxidation reactions, like alcohols,
unidentified impurities with unknown toxicologi- ketones, aldehydes and carboxylic acids. All of these catego-
cal profiles during storage. ries of substances are reactive enough to undergo secondary
The safety of sensiva® SC 50 is ensured by this reactions which each other.
high purity grade of ethylhexylglycerin having an Additionally, 1,2-diols undergo oxidative cleavage reac-
extremely low impurity profile. Due to its patented tions, known as glycol cleavage. This reaction is often used
stabilization, this purity is ensured for the entire for structure determination of sugars. Ethylhexylglycerin is a
shelf-life of the material. Beyond that, sensiva® SC glycerol ether which bears both functional groups, ether and
50 has been used in toxicological studies showing diol, in the same molecule. This makes it sensitive to ageing
that no side effects coming from its few impurities reactions under the influence of air.
are to be expected. Fresh sensiva® SC 50 shows a purity of more than 99%,
sensiva® SC 50-grade ethylhexylglycerin does which is exceptionally high for cosmetic raw materials.
not pose an increased risk for acquiring a contact To keep this purity for the entire shelf-life, schülke has
allergy after exposure. This was proven in sensi- developed a protection technology utilizing stabilizers, like
tization assays to determine the allergic potential antioxidants.
according to Magnusson-Kligman and a local As incompatibilities with the skin, such as irritations and
lymph node assay (LLNA). sensitization, are the most threatening side effects of the use
Other qualities of ethylhexylglycerin without of cosmetic products, stability of the raw materials, as well as
stabilization are now available to the personal care finished products, is of essential importance. Figure 1 shows
market. Depending on the origin, a significant a gas chromatogram of freshly distilled ethylhexylglycerin.
portion of unknown impurities can be present in Aside from the main peak, there are just a few very small
the fresh material. Additionally, these variants may signals that represent by-products and impurities in an
not guarantee a constant quality. Due to the ether- amount of less than 200 ppm each. Due to the stabilization
Save to
My Library function, decomposition can occur in unstabilized technology, sensiva® SC 50 retains this low impurity profile
ethylhexylglycerin. Thus, more impurities with for its entire shelf-life of three years.
CT1505_SPContent_Form_Schulke_fcx.indd 86 4/13/15 2:56 PM

Sponsored Content
Figure 2 shows
the chromatogram of Figure 1. Gas chromatogram of fresh ethylhexylglycerin
aged, unstabilized eth-
ylhexylglycerin. Many
additional peaks can
be seen, representing
unknown degrada-
tion products with an
amount of up to
2.5 %. The well-
defined material has
changed to a complex
mixture of potentially
critical substances.
Conclusion
Ethylhexylglycerin
becomes a very stable
molecule when it
is stabilized with
tocopherol. The safety
of sensiva® SC 50, the
Time (min)
stabilized quality of
ethylhexylglycerin,
has been tested and Figure 2. Gas chromatogram of aged, unstabilized ethylhexylglycerin
proven in comprehen-
sive toxicity studies by
schülke. The constant
purity guarantees
that no degradation
products develop
during storage for a
minimum of three
years.
Unstabilized, aged
ethylhexylglycerin
shows many break-
down products that
can develop during
storage. Unidenti-
fied impurities with
unknown toxico-
logical profile can
negatively influence
the safety of the
product.
The use of ethyl-
hexylglycerin in cosmetic products is increasing steadily, Disclaimer:
resulting in a higher exposure to consumers. To insure the Cosmetics & Toiletries occasionally seeks sponsored content—material that
safety of the consumer, it is of prime importance to verify has been created, provided, or influenced by the named sponsor—from
the quality of ethylhexylglycerin and to ensure the stability industry organizations, suppliers and other leaders dedicated to providing
relevant information to industry professionals. Although there is a commercial
over the entire shelf-life of the finished product. This is guar- benefit for Cosmetics & Toiletries, sponsored content also brings you, the user,
anteed by the use of sensiva® SC 50 with schülke’s patented useful industry information. Cosmetics & Toiletries takes meaningful steps to
ensure that you will not confuse sponsored content with content produced by
stabilization system. Cosmetics & Toiletries and governed by its editorial policy.
CT1505_SPContent_Form_Schulke_fcx.indd 87 4/13/15 2:56 PM

Advertiser Index | C&T
A&E Connock Ltd. Custom Ingredients MMP, Inc.

C2 20 53
sales@connock.com sales@custoblend.com sales.us@mmpinc.com
www.connock.co.uk www.custoblend.com www.mmpinc.com
AAK Personal Care Dr Straetmans Chem. Prod. GmbH Nikko Chemicals Co. Ltd.
58 42 C3
lipid@aak.com info@dr-straetmans.de www.nikkol.co.jp
www.aakpersonalcare.com www.dr-straetmans.de
(p. 16) Pilot Chemical Co.
61
Dupont Tate & Lyle BioProducts info@pilotchemical.com
43
Air Products & Chemicals, Inc. www.duponttateandlyle.com www.pilotchemical.com
50
www.airproducts.com/skin
Evonik Reed Exhibitions /in-cosmetics
31 83
AMA Laboratories, Inc. personal-care@evonik.com Brasil
26
www.amalabs.com www.evonik.com/personal-care www.in-cosmeticsbrasil.com
(p. 17)
Arista Industries, Inc. Reed Exhibitions/in-cosmetics
67 63
info@aristaindustries.com Extracts & Ingredients Korea
4
www.aristaindustries.com dfondots@morretec.com ivan.rahal@reedexpo.co.uk
www.morretec.com www.in-cosmeticskorea.com/visit
BASF
28
yvonne.specht@basf.com Floratech Rossow USA
15 73
www.carecreations.basf.com sales@floratech.com contact@rossow-usa.com
(p. 67) www.floratech.com www.rossow-usa.com
Berjé, Inc. Gattefossé SA Sabinsa Corp.
3 55 72
berje@berjeinc.com www.gattefosse.com info@sabinsa.com
www.berjeinc.com www.sabinsacosmetics.com
Grant Industries
1
Beraca Ingredients info@grantinc.com SCC California/Suppliers’ Day
80 www.grantinc.com 70
www.beraca.com www.caliscc.org
Bio-Botanica, Inc. Ichimaru Pharcos Co. Ltd. SCC New York/Anniversary Event
35 41 74
www.bio-botanica.com gifu@ichimaru.co.jp www.nyscc.org
www.ichimaru.co.jp
Bioland Ltd. schülke, Inc.
19 86
bioland@biolandkorea.com IDEA Tests info@schuelke.com
82
www.biolandkorea.com v.ribiere@groupeideatests.com www.schuelke.com
www.groupeideatests.com (p. 87)
Bloomage Freda Biopharm Co.
25
customer@bloomagefreda.com IFSCC Sederma France
77 51
www.bloomagefreda.com ifscc.scs@btconnect.com sederma-usa@croda.com
www.ifscc.org www.sederma.com
Brookfield Engineering Labs, Inc.
34
info@brookfieldengineering.com Ikeda Corp. (p. 12, 16)
75
www.brookfieldengineering.com info@ikeda-america.com Shin Etsu Silicones Of America
www.ikeda-corp.co.jp 49
cosmetics@shinetsusilicones.com
Campo Research Pte Ltd.
44
sales@campo-research.com Innospec Ltd. www.shinetsusilicones.com
13
www.campo-research.com americas-pc@innospecinc.com Silab
(p. 45) www.innospecinc.com 21
silab@silab.fr
Centerchem, Inc. INOLEX, Incorporated www.silab.fr
C4
cosmetics@centerchem.com 11
cheminfo@inolex.com (p. 16)
www.centerchem.com www.inolex.com Sinerga
39
Clariant International Ltd. Kemin Industries, Inc. info@sinerga.it
37
info@clariant.com 84
www.kemin.com www.sinerga.it
www.personalcare.clariant.com (p. 85) Summit Events/London 2015
65
Corum, Inc. Lipo Chemicals, Inc. info@summit-events.com
59
james.lee@corum.com.tw 9
www.lipochemicals.com www.summit-events.com
www.corum.com.tw Sytheon Ltd.
Lipotec, LLC 7
Cosmetics & Toiletries Summit 47
salesoffice@lipotec.com info@sytheonltd.com
79
ctsummit@allured.com www.lipotec.com www.sytheonltd.com
Summit.CosmeticsandToiletries.com (p. 64, 67, 69)
(p. 81) Lubrizol
57
www.lubrizol.com/personalcare Vevy Europe SpA
62
Cosphatec GmbH info@vevy.com
27
info@cosphatec.com Lucas Meyer Cosmetics www.vevy.com
33
www.cosphatec.com info@lucasmeyercosmetics.com
www.lucasmeyercosmetics.com Wacker Silicones Corp.
5
Croda, Inc. info.usa@wacker.com
23
marketing-usa@croda.com Mibelle AG Biochemistry www.wacker.com/personal-care
29
www.crodausa.com info@mibellebiochemistry.com
www.mibellebiochemistry.com Welch Holme & Clark Co., Inc.
(p. 17, 67) 69
www.welch-holme-clark.com
CT1505_Advertiser_Index_fcx.indd 88 4/21/15 10:18 AM

Untitled-1 1 4/9/15 9:42 AM
EF F NE
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Email: info.pc-na@dsm.com confirmed its anti-wrinkle efficacy and delivered new results. After only
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Untitled-1 1 4/1/15 11:25 AM

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May 2015

Natural Preservatives to Maintain Microflora p 22

Sea Anemone Delivery of Collagen, γ-PGA p 54

C&T Summit is getting closer! p 81

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NATURE’S FINEST EXFOLIANTS

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WHEN LOOK, FEEL AND PERFORMANCE

NYSCC SUPPLIERS’ DAY

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Eric Abrutyn Prithwiraj Maitra, Leslie C. Smith,

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S. Peter Foltis, Sylvianne Xiao Wu, PhD

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Beauty Industry Growth:

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Coconut Milk Moisture

Coconut for Curls

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INNOSPEC can help find the

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New Zealand-based Manuka Health introduced

Johnson & Johnson added a 5%

Active Ingredients: Minoxidil 5% w/w (without

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