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J Tifs 2010 08 003 PDF
J Tifs 2010 08 003 PDF
Review
Encapsulation of
polyphenols e phase or payload. On the other hand, the packaging mate-
rials are called coating material, wall material, capsule,
membrane, carrier or shell, which can be made of sugars,
a review gums, proteins, natural and modified polysaccharides,
lipids and synthetic polymers (Gibbs, Kermasha, Alli, &
Mulligan, 1999; Mozafari, 2006)
Zhongxiang Fanga,b,* and Microcapsules are small vesicles or particulates that may
Bhesh Bhandaria range from sub-micron to several millimeters in size
(Dziezak, 1998). Many morphologies can be produced for
a
School of Land, Crop and Food Sciences, encapsulation, but two major morphologies are more com-
The University of Queensland, Brisbane, monly seen (Fig. 1): one is mononuclear capsules, which
Qld 4072, Australia have a single core enveloped by a shell, while the other
b is aggregates, which have many cores embedded in a matrix
School of Biosystems Engineering and Food Science,
(Schrooyen, van der Meer, & De Kruif, 2001). Their spe-
Zhejiang University, Hangzhou 310029, China
cific shapes in different systems are influenced by the pro-
(School of Land, Crop and Food Sciences, The
cess technologies, and by the core and wall materials from
University of Queensland, Brisbane, Qld 4072,
which the capsules are made.
Australia. Tel.: D61 7 33469187;
Various techniques are used for encapsulation. In gen-
e-mail: z.fang2@uq.edu.au)
eral, three steps are involved in the encapsulation of bioac-
tive agents: (i) the formation of the wall around the material
Research on and the application of polyphenols, have recently to be encapsulated; (ii) ensuring that undesired leakage
attracted great interest in the functional foods, nutraceutical and does not occur; (iii) ensuring that undesired materials are
pharmaceutical industries, due to their potential health benefits kept out (Gibbs et al., 1999; Mozafari et al., 2008). The
to humans. However, the effectiveness of polyphenols depends current encapsulation techniques include spray drying,
on preserving the stability, bioactivity and bioavailability of the spray cooling/chilling, extrusion, fluidized bed coating, co-
active ingredients. The unpleasant taste of most phenolic com- acervation, liposome entrapment, inclusion complexation,
pounds also limits their application. The utilization of encapsu- centrifugal suspension separation, lyophilization, cocrystal-
lated polyphenols, instead of free compounds, can effectively lization and emulsion, etc. (Augustin & Hemar, 2009;
alleviate these deficiencies. The technologies of encapsulation Desai & Park, 2005; Gibbs et al., 1999).
of polyphenols, including spray drying, coacervation, liposome The main objective of encapsulation is to protect the
entrapment, inclusion complexation, cocrystallization, nanoen- core material from adverse environmental conditions,
capsulation, freeze drying, yeast encapsulation and emulsion, such as undesirable effects of light, moisture, and oxygen,
are discussed in this review. Current research, developments thereby contributing to an increase in the shelf life of the
and trends are also discussed. product, and promoting a controlled liberation of the encap-
sulate (Shahidi & Han, 1993). In the food industry, the
microencapsulation process can be applied for a variety
Introduction
of reasons, which have been summarized by Desai and
Microencapsulation, developed approximately 60 years
Park (2005) as follows: (i) protection of the core material
ago, is defined as a technology of packaging solids, liquids,
from degradation by reducing its reactivity to its outside en-
or gaseous materials in miniature, sealed capsules that can
vironment; (ii) reduction of the evaporation or transfer rate
release their contents at controlled rates under specific con-
of the core material to the outside environment; (iii) mod-
ditions (Desai & Park, 2005; Vilstrup, 2001). The packaged
ification of the physical characteristics of the original mate-
materials can be pure materials or a mixture, which are also
rial to allow easier handling; (iv) tailoring the release of the
called coated material, core material, actives, fill, internal
core material slowly over time, or at a particular time; (v) to
mask an unwanted flavor or taste of the core material; (vi)
* Corresponding author. dilution of the core material when only small amounts are
0924-2244/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tifs.2010.08.003
Z. Fang, B. Bhandari / Trends in Food Science & Technology 21 (2010) 510e523 511
from grape seeds (Zhang, Mou, & Du, 2007). The ratio of 333, showed a lower degradation of its polyphenol content
core substance to wall material was 30:70 w/w, while the and lower reduction of its antioxidant activity, suggesting
concentration of the slurry was 20% w/v. The encapsulation that the correct selection of the drying excipients is an im-
efficiency was up to 88.84%, and the procyanidin was not portant step in guaranteeing the stability and the quality of
changed during drying. The stability of the products was ob- the finished product. The results also indicated that the inlet
viously improved by spray drying. gas temperature had a significant effect on the total poly-
Chitosan has also been used as a wall material in spray phenol, protein and genistein contents of the dried extracts
drying of olive leaf extract (OLE) (Kosaraju, D’ath, & (Georgetti et al., 2008). Another wall material successfully
Lawrence, 2006). The loading percent of polyphenolic used for encapsulation of polyphenol was protein-lipid (so-
compounds was 27%, and the OLE-loaded microspheres dium caseinate-soy lecithin) emulsion, which has been used
normally had a smooth surface morphology. The FTIR in spray drying of grape seed extract, apple polyphenol ex-
spectroscopy results indicated that the majority of the tract and olive leaf extract (Kosaraju, Labbett, Emin,
OLE in the chitosan microsphere were physically encapsu- Konczak, & Lundin, 2008). Optical microscopy and parti-
lated in the chitosan matrix. Chiou and Langrish (2007) in- cle size distribution analysis indicated that the encapsulated
troduced citrus fruit fiber as an encapsulating agent for particles all had spherical morphology and uniform size
spray drying of bioactives extracted from Hibiscus sabdar- distribution. Radical scavenging activity studies demon-
iffa L. The main bioactive compounds in H. sabdariffa L. strated a significant retention of antioxidant activity after
extract are polyphenols, or more specifically, the anthocya- encapsulation by the spray-drying process (Kosaraju
nin complexes. The presence of the bioactive material in et al., 2008).
the fibers did not appear to significantly affect the product
size or shape. The results demonstrated that natural fruit Coacervation
fibers might be a potential replacement carrier for spray The concept behind coacervation microencapsulation is
drying sticky materials. This encapsulation process com- the phase separation of one or many hydrocolloids from
bined two products (fruit fiber and polyphenols) into one the initial solution and the subsequent deposition of the
multipurpose functional food, creating a novel nutraceutical newly formed coacervate phase around the active ingredi-
product suitable for a variety of applications in functional ent suspended or emulsified in the same reaction media
food manufacturing (Chiou & Langrish, 2007). (Gouin, 2004). Coacervation encapsulation can be achieved
More recently, the effects of drying aids comprising col- simply with only one colloidal solute such as gelatin, or
loidal silicon dioxide (tixosil 333), maltodextrin and starch through a more complex process, for example, with gelatin
on spray drying of soybean extract have been studied and gum acacia. Complex coacervation is usually associ-
(Georgetti, Casagrande, Souza, Oliveira, & Fonseca, ated with no definite forms (Fig. 2), and is considered an
2008). The resulting product, to which was added tixosil expensive method for encapsulating food ingredients
Z. Fang, B. Bhandari / Trends in Food Science & Technology 21 (2010) 510e523 513
Fig. 2. Illustration of the characteristics of encapsulated polyphenolic capsules produced by various encapsulation processes.
(Gouin, 2004); however, this process should be related to chitosan. The polyphenols can be retained in a chitosan-al-
the potential benefits it might offer, especially to high- ginate membrane, but maximum release in water was
value, labile functional ingredients, such as the encapsula- achieved in a shorter time for chitosan coated beads than
tion of polyphenols. with the alginate beads. These results implied that the
Yerba mate (Ilex paraguariensis) extract (containing wall materials can affect the release of the natural antioxi-
62.11 1.16 mg of gallic acid/g yerba mate) has been en- dants of yerba mate.
capsulated with two different systems: calcium alginate and Gelatin is a protein containing many glycine, proline and
calcium alginate-chitosan (Deladino, Anbinder, Navarro,& 4-hydroxyproline residues. A new type of protein/polyphe-
Martino, 2008). A high load of active compound (>85%) nol microcapsule based on ()-epigallocatechin gallate
was obtained in the alginate beads but in chitosan coated (EGCG) and gelatin (type A), has been produced using
beads the entrapment was lower (around 50%), on account the layer-by-layer (LbL) assembly method (Shutava,
of the active compound being lost during immersion in Balkundi, & Lvov, 2009). The first layer was a gelatin layer
514 Z. Fang, B. Bhandari / Trends in Food Science & Technology 21 (2010) 510e523
over the MnCO3 microcores, over which an EGCG layer Mozafari & Mortazavi, 2005; Mozafari et al., 2008;
was formed by adding EGCG solution to the gelatin-coated Watwe & Bellare, 1995). A variety of liposome techniques
microparticles. The MnCO3 microcores were dissolved in have been employed for the encapsulation of polyphenols.
EDTA solution to form the stable (Gel A/EGCG)4 capsules. Fan, Xu, Xia, and Zhang (2007) compared the effects of
The EGCG content of the protein/polyphenol film material five different liposome methods on the encapsulation of sal-
was as high as 30% w/w, while the EGCG in the LbL as- idroside e thin film evaporation, sonication, reverse phase
semblies retained its antioxidant activity (Shutava, evaporation, melting, and freezing-thawing. Multilamellar
Balkundi & Lvov, 2009). vesicles can be obtained by thin film evaporation, larger
Glucan is a polysaccharide, and also a thermoreversible unilamellar vesicles by reverse phase evaporation, and
gelling agent, whose gelling behavior depends on its molec- small unilamellar vesicles by sonication or extrusion tech-
ular weight and concentration (Vaikousi, Biliaderis, & nique (Bangham et al., 1965; Cevce, 1993.). The freez-
Izydorczyk, 2004). During cooling of the glucan water so- ing-thawing treatment leads to the production of special
lution from 80 C to room temperature, a network structure freezing-thawing multilamellar vesicles (Maestrelli,
can be formed through an interaction of the chain segment Gonzalez-Rodriguez, Rabasco, & Mura, 2006). The encap-
association and aggregated junction zones (Morgan & sulating efficiency of liposomes is highest when they are
Ofman, 1998). Black currant extract has been encapsulated prepared by freezing-thawing, followed by thin film evapo-
in glucan by simply mixing with hot dispersed glucan gel, ration, then reverse phase evaporation, while melting and
followed by cooling and cutting into cubes, or being drop- sonication has the lowest efficiency. Loading capacity of
ped into oil to produce a bead morphology (Xiong, Melton, salidroside can have significant effects on encapsulating
Easteal, & Siew, 2006). Recovery of 73e79% of encapsu- efficiency, average diameter, and z potential of liposomes.
lated anthocyanins was achieved using normal oven drying Liposomal systems prepared by sonication, melting, and re-
to dehydrate the gel matrix. Larger amounts of anthocya- verse phase evaporation, displayed better dispersivity. Sali-
nins were released from cubes than from beads using the droside liposomes show a slower increase in particle size
same drying process. The encapsulated anthocyanins ex- than liposomes without salidroside, suggesting salidroside
hibited little difference as free radical scavengers, with an plays an important role in preventing the aggregation and
increase in their reducing ability with time. fusion of liposomes. Fan et al. (2007) illustrated that these
Other coacervation coating systems such as gliadin, hep- differences might come from the different morphologies of
arin/gelatin, carrageenan, soy protein, polyvinyl alcohol, liposomes prepared by different methods.
gelatin/carboxymethylcellulose, b-lactoglobulin/gum aca- The nature of the core materials is another factor that af-
cia, and guar gum/dextran have also been studied (Gouin, fects the efficiency of liposome encapsulation. The isomers
2004). However, most of the core materials in these studies of (þ)-catechin and ()-epicatechin entrapped in lipo-
were essential oils rather than polyphenols. somes show similar encapsulation levels and release rates
(Fang, Hwang, Huang, & Fang, 2006). However, another
Liposomes type of catechin, ()-epigallocatechin-3-gallate (EGCG),
Liposomes were first described by Bangham and co- has been observed to have a much higher level of encapsu-
workers in 1965 at Cambridge University (Bangham, lation for the same liposome system. EGCG contains a gal-
Standish, & Watkins, 1965). They are colloidal particles con- loyl group, indicating a greater lipophilicity. Hence it is
sisting of a membranous system formed by lipid bilayers en- possible that EGCG was stronger when to locate within
capsulating aqueous space(s) (Fig. 2). Owing to the the liposome bilayers, thereby increasing the entrapment.
possession of both lipid and aqueous phases, liposomes Liposome encapsulation efficiency can be increased by
can be utilized in the entrapment, delivery, and release of wa- the addition of ethanol (15%) to the preparation hydration
ter soluble, lipid-soluble, and amphiphilic materials. The un- solution (Fang, Lee, Shen, & Huang, 2006). In response,
derlying mechanism for the formation of liposomes and the core material of EGCG in the liposomes showed
nanoliposomes is basically a hydrophilicehydrophobic in- a high rate of encapsulation of nearly 100%, compared to
teraction between phospholipids and water molecules. A ma- 84.6% encapsulation for conventional liposome. It was
jor advantage of their use is the ability to control the release also shown that ethanolic solutions of phospholipids exhibit
rate of the incorporated materials and deliver them to the high encapsulation efficiency for both hydrophilic and lipo-
right place at the right time (Schäfer et al., 1992). Bioactive philic actives (Dayan & Touitou, 2000). The liposomes
agents encapsulated into liposomes can be protected from di- made in the presence of ethanol had a relatively small
gestion in the stomach, and show significant levels of absorp- size of 133.1 nm. The further addition of deoxycholic
tion in the gastrointestinal tract, leading to the enhancement acid (DA) significantly increased the size of the vesicles
of bioactivity and bioavailability (Takahashi et al., 2007). to 378.2 nm. EGCG encapsulated in liposomes with ethanol
There are several methods for producing liposomes, and and DA gave a 20 fold increase in active deposition in basal
there are a number of excellent books and published re- cell carcinomas relative to the free form (Fang et al., 2006).
views that provide details of the most common production The larger vesicle size of this formulation was suggested to
techniques (Betageri & Kulkarni, 1999; Frezard, 1999; be the predominant factor governing this enhancement.
Z. Fang, B. Bhandari / Trends in Food Science & Technology 21 (2010) 510e523 515
affinity of modified cyclodextrins (Lucas-Abellán, Fortea, extract containing caffeoyl derivatives and flavonoids, by
& Gabaldón, 2008) cocrystallization in a supersaturated sucrose solution. The
To illustrate the structures of polyphenol-CD inclusion co-crystallized product had a typically cluster-like agglom-
complexes, some advanced analytical instruments were ap- erate structure with void spaces and a sucrose crystal size
plied. The spatial configuration of the complex of rutin with varying between 2 and 30 mm. An extra layer of a network
b-CD has been proposed, based on NMR and molecular mod- with neat edges covered the crystals. The microstructure
eling (Ding et al., 2003), which revealed that the binding site was further confirmed by differential scanning calorimetry,
for rutin is a single ring of rutin molecule penetrating into the X-ray diffraction and scanning electron microscopy
b-CD cavity in the shallow position, forming a 1:1 inclusion (Deladino, Navarro, & Martino, 2010). The cocrystallization
complex. This structure can be confirmed by 1H NMR and cir- of yerba mate extract changed it from a cohesive material to
cular dichroism spectroscopy (Calabrò et al., 2005). The struc- be a non-cohesive product, and notably reduced its hygro-
ture of the inclusion complex of ferulic acid (FA) with a-CD scopic characteristics without affecting its high solubility;
has been analyzed by rotating frame nuclear overhouser effect this demonstrated that cocrystallization is a good alternative
spectroscopy (ROESY) (Anselmi et al., 2008). Based on this for the preservation and handling of yerba mate extract for
technology and modeling simulation, the insertion of the FA further application in food products. There have been very
into the lipophilic interior of a-CD involves the -COOH and few reports of the application of the cocrystallization
a, b-unsaturated groups and part of its aromatic moiety. The process.
phenol and methoxyl groups of FA lie on the plane of the wider
rim. This encapsulation increases the photo-stability of FA, Nanoencapsulation
slows FA release, and would provide safer and longer-lasting Nanoencapsulation involves the formation of active-
protection of the skin against solar radiation, if applied in cos- loaded particles with diameters ranging from 1 to
metic formulations (Anselmi et al., 2008) 1000 nm (Reis, Neufeld, Ribeiro, & Veiga, 2006). The
With the exception of CDs, other types of biopolymers term nanoparticle is a collective name for both nano-
have been employed in the molecular inclusion of polyphe- spheres and nanocapsules. Nanospheres have a matrix
nols, such as curcumin being encapsulated in hydrophobi- type of structure. Actives may be absorbed at the sphere
cally modified starch (HMS) (Yu & Huang, 2010). The surface or encapsulated within the particle. Nanocapsules
complexed curcumin showed a 1670 fold increase in solu- are vesicular systems in which the active is confined to
bility, possibly reflecting the hydrophobic interaction and a cavity consisting of an inner liquid core surrounded by
hydrogen bonding between curcumin and HMS. The encap- a polymeric membrane (Fig. 2) (Couvreur, Dubernet, &
sulated curcumin revealed enhanced in vitro anti-cancer ac- Puisieux, 1995). The active substances are usually dis-
tivity compared to the free form. solved in the inner core but may also be adsorbed to the
capsule surface (Allémann, Gurny, & Doekler, 1993). It
Cocrystallization is proposed that any target actives, while incorporated
Co-crystallization is an encapsulation process in which the into a complex of polymers, which result in nanoscale-
crystalline structure of sucrose is modified from a perfect to an sized particles, might be called ‘encapsulated nanopar-
irregular agglomerated crystal, to provide a porous matrix in ticles’. Compared to micron-sized particles, nanoparticles
which a second active ingredient can be incorporated (Chen, provide a greater surface area and have the potential to in-
Veiga, & Rizzuto, 1988). Spontaneous crystallization of super- crease solubility due to a combination of large interfacial
saturated sucrose syrup is achieved at high temperature (above adsorption of the core compound, enhanced bioavailabil-
120 C) and low moisture (95e97 Brix). If a second ingredi- ity, improved controlled release, which enable better pre-
ent is added at the same time, the spontaneous crystallization cision targeting of the encapsulated materials (Mozafari
results in the incorporation of the second ingredient into the et al., 2008). A variety of techniques have been employed
void spaces inside the agglomerates of the microsized crystals to develop polyphenol nanoparticles.
(Fig. 2), with a size less than 30 mm (Bhandari, Datta, D’Arcy, Barras et al. (2009) describe the loading of quercetin and
& Rintoul, 1998). The main advantages of cocrystallization EGCG by lipid nanocapsules (LNC) through the applica-
are improved solubility, wettability, homogeneity, dispersibil- tion of the phase inversion process. Briefly, the actives
ity, hydration, anticaking, stability and flowability of the en- were mixed in the oil phase prior to preparation. Soybean
capsulated materials (Beristain, Vázquez, Garcı́a, & Vernon- lecithin, surfactant, NaCl and distilled water were then
Carter, 1996). Other advantages are that the core materials mixed and heated to form a W/O emulsion. The mixture
in a liquid form can be converted to a dry powdered form was cooled, and distilled cold water (0 C) added, with stir-
without additional drying, and the products offer direct tablet- ring to form O/W nanocapsules. The benefits of this method
ing characteristics because of their agglomerated structure, are that the average volume sizes of particles are a function
and thus offer significant advantages to the candy and pharma- of the formulation composition, which means the LNC size
ceutical industries (Desai & Park, 2005). can be tailored by formulation design. The higher encapsu-
Deladino, Anbinder, Navarro, and Martino (2007) re- lated quercetin LNC increased its apparent aqueous solubil-
ported on the encapsulation of yerba mate (I. paraguariensis) ity by a factor of 100. The encapsulated quercetin and
Z. Fang, B. Bhandari / Trends in Food Science & Technology 21 (2010) 510e523 517
()-EGCG have proved to be more stable compared to the (Shao et al., 2009). The mPEGePCL based nanoparticles
free ones. are composed of a hydrophilic segment and a hydrophobic
The nanoprecipitation technique has been used for cur- segment, which are capable of loading the target active by
cumin entrapment, based on poly (lactide-co-glycolide) self assembling into nanoscale spherical structures with
(PLGA) and a stabilizer polyethylene glycol (PEG)-5000 a hydrophilic outer shell and a hydrophobic inner core
(Anand et al., 2010). The nanoprecipitation technique in- (Liu et al., 2008). In this way, lipophilic actives can be en-
volves three steps: First, the target actives and a polymer trapped into the hydrophobic core of the nanosphere, while
are mixed in an organic solution; second, the mixture is its hydrophilic outer shell is maintained as a stabilizer for
added, drop wise, to an aqueous solution, normally contain- the system. Other actives with lipophilicity can also be in-
ing a surfactant; third, the resulting dispersion of nanopar- corporated into this nanoparticle system to enhance their
ticles is vacuum evaporated to eliminate the organic bioavailability.
solvent, and then centrifuged or filtered to obtain the parti- Tea catechins have been successfully encapsulated in chi-
cles. In the case of curcumin-loaded nanoparticles, the en- tosan- tripolyphosphate (CS-TPP) nanoparticles using a sim-
capsulation efficiency was reported to have reached 97.5%, ple ionotropic gelation method (Hu et al., 2008). By
with the particle diameter being about 80.9 nm, which en- controlling the critical fabricating parameters of the CS mo-
hanced its cellular uptake, and increased in vitro bioactivity, lecular mass, CS concentration, and CS-TPP mass ratio, de-
resulting in superior in vivo bioavailability over free curcu- sirable CS-TPP nanoparticles can be spontaneously formed
min (Anand et al., 2010). Other quercetin loaded nanopar- when the freshly prepared CS solution containing tea cate-
ticles were developed by using a similar technique, with chins is added with TPP solution, while stirring at room tem-
a particle size of <85 nm, and encapsulation efficiency of perature (Hu et al., 2008). In comparison with this simple
over 99% (Wu et al., 2008). The encapsulated active of method, a relatively complicated method has been developed
quercetin might have an amorphous state, which formed in- for the encapsulation of polyphenols of EGCG, tannic acid,
termolecular hydrogen bonding with carriers. The release curcumin, and theaflavin (Shutava, Balkundi, Vangala et al.,
of the nanoparticals was 74-fold times higher when com- 2009). First, gelatin nanoparticles are prepared using a two-
pared with the pure active, and possessed more effective an- step desolvation method. These particles are then further
tioxidant activities. encapsulated in polyelectrolytes using a layer-by-layer shell
A method based on the concept of emul- assembly method. Finally, the polyphenols are loaded into
sionediffusioneevaporation, using polyethylene glycol the prepared nanoparticles by adsorption under certain pH
(PEG) 400 as a co-solvent, has been applied on ellagic values. The adsorption of polyphenols to the nanoparticles
acid (EA) loaded PLGA nanoparticles (Bala, Bhardwaj, depends on the chemical nature of the molecules. Adsorption
Hariharan, Kharade, Roy, & Ravi Kumar, 2006). Didode- of polyphenols with higher molecular weights and a larger
cyldimethylammomium bromide (DMAB) and polyvinyl number of phenolic -OH groups was found to be higher.
alcohol (PVA), alone and in combination with chitosan The amount of theaflavin, the polyphenol with the highest
(CS), were used as the stabilizer. The basis of this technique molecular weight among those investigated, was as high as
is as follows: the stirring of the EA-PLGA-PEG 400 mix- 70% of the mass of nanoparticle solid material. Loading of
ture causes the dispersion of the solvent in the form of ir- tannic acid and EGCG is lower, while it is almost negligible
regularly sized droplets in equilibrium with the for curcumin (Shutava, Balkundi, Vangala et al., 2009).
continuous phase, while the stabilizer is adsorbed on to
the larger interface, thereby creating the first emulsion Freeze drying
stage; then, the homogenization results in smaller droplets Freeze drying, also known as lyophilization or cryode-
with more homogenous size distribution; the addition of siccation, is a process used for the dehydration of almost
water and subsequent heating destabilizes the equilibrium all heat-sensitive materials and aromas. Freeze-drying
and causes the organic solvent to diffuse into the aqueous works by freezing the material and then reducing the sur-
phase and then out of the system, leading to precipitation rounding pressure and adding enough heat, to allow the fro-
of the polymer along with the active as very small particles zen water in the material to sublimate directly from the
(Kumar, Bakowsky, & Lehr, 2004). The initial release of solid phase to the gas phase (Oetjen & Haseley, 2004). En-
EA from nanoparticles in pH 7.4 phosphate buffer is rapid, capsulation by freeze drying is achieved as the core
followed by a slower sustained release. An in situ intestinal materials homogenize in matrix solutions and then co-ly-
permeability study in rats showed a higher uptake of active ophilize, usually resulting in uncertain forms (Fig. 2).
encapsulated in nanoparticles prepared using PVA, Except for the long dehydration period required (generally
PVAeCS blend and DMAB as stabilizers, than pure active 20 h), freeze-drying is a simple technique for encapsulating
(Bala et al., 2006). water-soluble essences and natural aromas, as well as drugs
Resveratrol is incorporated into amphiphilic copolymers (Desai & Park, 2005). Freeze dried samples of pomace con-
of mPEGePCL (methoxy poly(ethylene glycol)-poly(cap- taining anthocyanin and maltodextrin DE20 have shown
rolactone)), with an active loading content of good shelf life stability during storage at 50 C/0.5 water
19.4 2.4% and an encapsulation efficiency of >90% activity for up to two months (Delgado-Vargas, Jimenez,
518 Z. Fang, B. Bhandari / Trends in Food Science & Technology 21 (2010) 510e523
Bhandari, B. R., D’Arcy, B. D., & Padukka, I. (1999). Encapsulation of with rutin. Spectrochimica Acta Part A: Molecular and Biomolec-
lemon oil by paste method using b-cyclodextrin: encapsulation ular Spectroscopy, 59, 3421e3429.
efficiency and profile of oil volatiles. Journal of Agricultural and Dziezak, J. D. (1998). Microencapsulation and encapsulated food in-
Food Chemistry, 47, 5194e5197. gredients. Food Technology, 42, 136e151.
Bhandari, B. R., Datta, N., D’Arcy, B. R., & Rintoul, G. B. (1998). Co- Ersus, S., & Yurdagel, U. (2007). Microencapsulation of anthocyanin
crystallization of honey with sucrose. Lebensmittel-Wissenschaft pigments of black carrot (Daucus carota L.) by spray drier. Journal
und-Technologie, 31, 138e142. of Food Engineering, 80, 805e812.
Bishop, J. R. P., Nelson, G., & Lamb, J. (1998). Microencapsulation in Fan, M. H., Xu, S. Y., Xia, S. Q., & Zhang, X. M. (2007). Effect of
yeast cells. Journal of Microencapsulation, 15, 761e773. different preparation methods on physicochemical properties of
Blanquet, S., Garrait, G., Beyssac, E., Perrier, C., Denis, S., salidroside liposomes. Journal of Agricultural and Food Chemistry,
Hébrard, G., et al. (2005). Effects of cryoprotectants on the viability 55, 3089e3095.
and activity of freeze dried recombinant yeasts as novel oral drug Fang, J.-Y., Hwang, T.-L., Huang, Y.-L., & Fang, C.-L. (2006).
delivery systems assessed by an artificial digestive system. Euro- Enhancement of the transdermal delivery of catechins by liposomes
pean Journal of Pharmaceutics and Biopharmaceutics, 61, 32e39. incorporating anionic surfactants and ethanol. International Journal
Calabrò, M. L., Tommasini, S., Donato, P., Stancanelli, R., Raneri, D., of Pharmaceutics, 310, 131e138.
Catania, S., et al. (2005). The rutin/ b-cyclodextrin interactions in fully Fang, J.-Y., Lee, W.-R., Shen, S.-C., & Huang, Y.-L. (2006). Effect of
aqueous solution: spectroscopic studies and biological assays. Jour- liposome encapsulation of tea catechins on their accumulation in
nal of Pharmaceutical and Biomedical Analysis, 36, 1019e1027. basal cell carcinomas. Journal of Dermatological Science, 42,
Calabrò, M. L., Tommasini, S., Donato, P., Raneri, D., Stancanelli, R., 101e109.
Ficarra, P., et al. (2004). Effects of a- and b-cyclodextrin com- Fang, J.-Y., Hung, C.-F., Liao, M.-H., & Chien, C.-C. (2007). A study of
plexation on the physico-chemical properties and antioxidant ac- the formulation design of acoustically active lipospheres as carriers
tivity of some 3-hydroxyflavones. Journal of Pharmaceutical and for drug delivery. European Journal of Pharmaceutics and Bio-
Biomedical Analysis, 35, 365e377. pharmaceutics, 67, 67e75.
Cevce, G. (1993). Lipid properties as a basis for membrane modeling and Flanagan, J., & Singh, H. (2006). Microemulsions: a potential delivery
rational liposome design. In G. Gregoriadis (Ed.) (2nd ed.).Liposome system for bioactives in food. Critical Reviews in Food Science and
technology, Vol. 1 (pp. 1e36) Boca Raton: CRC Press. Nutrition, 46, 221e237.
Chen, A. C., Veiga, M. F., & Rizzuto, A. B. (1988). Cocrystallization: an Frezard, F. (1999). Liposomes: from biophysics to the design of peptide
encapsulation process. Food Technology, 11, 87e90. vaccines. Brazilian Journal of Medical and Biological Research, 32,
Chiou, D., & Langrish, T. A. G. (2007). Development and character- 181e189.
isation of novel nutraceuticals with spray drying technology. Jour- Friberg, S., Larsson, K., & Sjoblom, J. (2004). Food emulsions, (4th ed.).
nal of Food Engineering, 82, 84e91. New York: Marcel Dekker.
Chen, L., Remondetto, G. E., & Subirade, M. (2006). Food protein- Georgetti, S. R., Casagrande, R., Souza, C. R. F., Oliveira, W. P., &
based materials as nutraceutical delivery systems. Trends in Food Fonseca, M. J. V. (2008). Spray drying of the soybean extract: effects
Science & Technology, 17, 272e283. on chemical properties and antioxidant activity. LWT -Food
Couvreur, P., Dubernet, C., & Puisieux, F. (1995). Controlled drug Science and Technology, 41, 1521e1527.
delivery with nanoparticles: current possibilities and future trends. Gibbs, B. F., Kermasha, S., Alli, I., & Mulligan, C. N. (1999). Encap-
European Journal of Pharmaceutics and Biopharmaceutics, 41, sulation in the food industry: a review. International Journal of
2e13. Food Sciences and Nutrition, 50, 213e224.
Dayan, N., & Touitou, E. (2000). Carriers for skin delivery of trihexy- Gouin, S. (2004). Microencapsulation: industrial appraisal of existing
phenidyl HCl: ethosomes vs. liposomes. Biomaterials, 21, technologies and trends. Trends in Food Science and Technology,
1879e1885. 15, 330e347.
de Vos, P., Faas, M. M., Spasojevic, M., & Sikkema, J. (2010). Encapsu- Gradinaru, G., Biliaderis, C. G., Kallithraka, S., Kefalas, P., &
lation for preservation of functionality and targeted delivery of bio- Garcia-Viguera, C. (2003). Thermal stability of Hibiscus sabdariffa
active food components. International Dairy Journal, 20, 292e302. L. anthocyanins in solution and in solid state: effects of copig-
Deladino, L., Anbinder, P. S., Navarro, A. S., & Martino, M. N. (2007). mentation and glass transition. Food Chemistry, 83, 423e436.
Co-crystallization of yerba mate extract (Ilex paraguariensis) and Haslam, E. (1996). Natural polyphenols (vegetable tannins) as drugs:
mineral salts within a sucrose matrix. Journal of Food Engineering, possible modes of action. Journal of Natural Product, 59,
80, 573e580. 205e215.
Deladino, L., Anbinder, P. S., Navarro, A. S., & Martino, M. N. (2008). Haslam, E., & Lilley, T. H. (1988). Natural astringency in foodstuffsda
Encapsulation of natural antioxidants extracted from Ilex para- molecular interpretation. Critical Reviews of Food Science and
guariensis. Carbohydrate Polymers, 71, 126e134. Nutrition, 27, 1e40.
Deladino, L., Navarro, A. S., & Martino, M. N. (2010). Microstructure Hu, B., Pan, C., Sun, Y., Hou, Z., Ye, Y., Hu, B., et al. (2008). Opti-
of minerals and yerba mate extract co-crystallized with sucrose. mization of fabrication parameters to produce chitosan-tripoly-
Journal of Food Engineering, 96, 410e415. phosphate nanoparticles for delivery of tea catechins. Journal of
Delgado-Vargas, F., Jimenez, A. R., & Pardes-Lopez, O. (2000). Natural Agricultural and Food Chemistry, 56, 7451e7458.
pigments: carotenoids, anthocyanins and betalainsecharacteris- Jafari, S. M., Assadpoor, E., He, Y., & Bhandari, B. (2008). Encapsula-
tics, biosynthesis, processing and stability. Critical Reviews in Food tion efficiency of food flavours and oils during spray drying. Drying
Science and Nutrition, 40, 173e289. Technology, 26, 816e835.
Desai, K. G. H., & Park, H. J. (2005). Recent developments in micro- Khaled, Al-T., & Jagdish, S. (2007). Smart polymer based delivery
encapsulation of food ingredients. Drying Technology, 23, systems for peptides and proteins. Recent Patents on Drug Delivery
1361e1394. & Formulation, 1, 65e71.
Di Mattia, C. D., Sacchetti, G., Mastrocola, D., & Pittia, P. (2009). Kosaraju, S. L., D’ath, L., & Lawrence, A. (2006). Preparation and
Effect of phenolic antioxidants on the dispersion state and chemical characterisation of chitosan microspheres for antioxidant delivery.
stability of olive oil O/W emulsions. Food Research International, Carbohydrate Polymers, 64, 163e167.
42, 1163e1170. Kosaraju, S. L., Labbett, D., Emin, M., Konczak, I., & Lundin, L. (2008).
Ding, H., Chao, J., Zhang, G., Shuang, S., & Pan, J. (2003). Preparation Delivering polyphenols for healthy ageing. Nutrition & Dietetics,
and spectral investigation on inclusion complex of b-cyclodextrin 65, S48eS52.
522 Z. Fang, B. Bhandari / Trends in Food Science & Technology 21 (2010) 510e523
Kumar, M. N. V. R., Bakowsky, U., & Lehr, C. M. (2004). Preparation Priprem, A., Watanatorn, J., Sutthiparinyanont, S., Phachonpai, W., &
and characterization of cationic PLGA nanospheres as DNA car- Muchimapura, S. (2008). Anxiety and cognitive effects of quercetin
riers. Biomaterials, 25, 1771e1777. liposomes in rats. Nanomedicine: Nanotechnology, Biology, and
Laine, P., Kylli, P., Heinonen, M., & Jouppila, K. (2008). Storage stability Medicine, 4, 70e78.
of microencapsulated cloudberry (Rubus chamaemorus) phenolics. Quideau, S., & Feldman, K. S. (1996). Ellagitannin chemistry. Chemi-
Journal of Agricultural and Food Chemistry, 56, 11251e11261. cal Reviews, 96, 475e503.
Liu, B., Yang, M., Li, X., Qian, X., Shen, Z., Ding, Y., et al. (2008). Reis, C. P., Neufeld, R. J., Ribeiro, A. J., & Veiga, F. (2006). Nanoencapsula-
Enhanced efficiency of thermally targeted taxanes delivery in tion I. Methods for preparation of drug-loaded polymeric nanoparticles.
a human xenograft model of gastric cancer. Journal of Pharma- Nanomedicine: Nanotechnology, Biology, and Medicine, 2, 8e21.
ceutical Sciences, 97, 3170e3181. Scalbert, A., Johnson, I. T., & Saltmarsh, M. (2005). Polyphenols: an-
Lucas-Abellán, C., Fortea, M. I., Gabaldón, J. A., & Núñez tioxidants and beyond. American Journal of Clinical Nutrition, 81,
-Delicado, E. (2008). Encapsulation of quercetin and myricetin in 215Se217S.
cyclodextrins at acidic pH. Journal of Agricultural and Food Scalbert, A., Manach, C., Morand, C., Rémésy, C., & Jiménez, L.
Chemistry, 56, 255e259. (2005). Dietary polyphenols and the prevention of diseases. Criti-
Lucas-Abellán, C., Fortea, M. I., López-Nicolás, J. M., & Núñez- cal Reviews in Food Science and Nutrition, 45(20), 287e306.
Delicado, E. (2007). Cyclodextrins as resveratrol carrier system. Schäfer, V., von Briesen, H., Andreesen, R., Steffan, A. M., Royer, C.,
Food Chemistry, 104, 39e44. Tröster, S., et al. (1992). Phagocytosis of nanoparticles by human
Maestrelli, F., Gonzalez-Rodriguez, M. L., Rabasco, A. M., & Mura, P. immunodeficiency virus (HIV)-infected macrophages: a possibility
(2006). Effect of preparation technique on the properties of lipo- for antiviral drug targeting. Pharmaceutical Research, 9, 541e546.
somes encapsulating ketoprofen-cyclodextrin complexes aimed for Schrooyen, P. M. M., van der Meer, R., & De Kruif, C. G. (2001). Mi-
transdermal delivery. International Journal of Pharmaceutics, 298, croencapsulation: its application in nutrition. Proceedings of the
53e60. Nutrition Society, 60, 475e479.
Maheshwari, R. K., Singh, A. K., Gaddipati, J., & Srimal, R. C. (2006). Serozym Laboratories. (1973). French patent specification no. 2179528.
Multiple biological activities of curcumin: a short review. Life Shahidi, F., & Han, X. Q. (1993). Encapsulation of food ingredients.
Sciences, 78, 2081e2087. Critical Reviews in Food Science and Nutrition, 33, 501e547.
Manach, C., Scalbert, A., Morand, C., Rémésy, C., & Jiménez, L. Shao, J., Li, X., Lu, X., Jiang, C., Hu, Y., Li, Q., et al. (2009). Enhanced
(2004). Polyphenols: food sources and bioavailability. American growth inhibition effect of resveratrol incorporated into biode-
Journal of Clinical Nutrition, 79, 727e747. gradable nanoparticles against glioma cells is mediated by the in-
McClements, D. J. (2005). Food emulsions: Principles, practice, and duction of intracellular reactive oxygen species levels. Colloids
techniques, (2nd ed.). Boca Raton: CRC Press. and Surfaces B: Biointerfaces, 72, 40e47.
McClements, D. J., Decker, E. A., Park, Y., & Weiss, J. (2009). Structural Shi, G., Rao, L., Yu, H., Xiang, H., Pen, G., Long, S., et al. (2007). Yeast-
design principles for delivery of bioactive components in nutra- cell-based microencapsulation of chlorogenic acid as a water-sol-
ceuticals and functional foods. Critical Reviews in Food Science uble antioxidant. Journal of Food Engineering, 80, 1060e1067.
and Nutrition, 49, 577e606. Shutava, T. G., Balkundi, S. S., & Lvov, Y. M. (2009). ()-Epigalloca-
Micap Plc. (2004). Micro-organism microcapsules, UK patent appli- techin gallate/gelatin layer-by-layer assembled films and micro-
cation, GB2396107A. capsules. Journal of Colloid and Interface Science, 330, 276e283.
Mercader-Ros, M. T., Lucas-Abellán, C., Fortea, M. I., Gabaldón, J. A., Shutava, T. G., Balkundi, S. S., Vangala, P., Steffan, J. J., Bigelow, R. L.,
& Núñez-Delicado, E. (2010). Effect of HP-b-cyclodextrins com- Cardelli, J. A., et al. (2009). Layer-by-layer-coated gelatin nano-
plexation on the antioxidant activity of flavonols. Food Chemistry, particles as a vehicle for delivery of natural polyphenols. ACS
118, 769e773. Nano, 3, 1877e1885.
Morgan, K., & Ofman, J. (1998). Glucagel, a gelling b-glucan from Surh, Y. J. (2003). Cancer chemoprevention with dietary phytochemi-
barley. Cereal Chemistry, 75, 879e881. cals. Nature Reviews Cancer, 3, 768e780.
Mozafari, M. R. (2005). Liposomes: an overview of manufacturing Tang, B., Ma, L., Wang, H. Y., & Zhang, G. Y. (2002). Study on the
techniques. Cellular & Molecular Biology Letters, 10, 711e719. supramolecular interaction of curcumin and beta-cyclodextrin by
Mozafari, M. R. (2006). Bioactive entrapment and targeting using spectrophotometry and its analytical application. Journal of Agri-
nanocarrier technologies: an introduction. In M. R. Mozafari (Ed.), cultural and Food Chemistry, 50, 1355e1361.
Nanocarrier technologies: Frontiers of nanotherapy (pp. 1e16). Takahashi, M., Inafuku, K., Miyagi, T., Oku, H., Wada, K., Imura, T.,
The Netherlands: Springer. et al. (2007). Efficient preparation of liposomes encapsulating
Mozafari, M. R., Khosravi-Darani, K., Borazan, G. G., Cui, J., food materials using lecithins by a mechanochemical method.
Pardakhty, A., & Yurdugul, S. (2008). Encapsulation of food ingre- Journal of Oleo Science, 56, 35e42.
dients using nanoliposome technology. International Journal of Takahashi, M., Uechi, S., Takara, K., Asikin, Y., & Wada, K. (2009).
Food Properties, 11, 833e844. Evaluation of an oral carrier system in rats: bioavailability and
Mozafari, M. R., & Mortazavi, S. M. (2005). Nanoliposomes: From antioxidant properties of liposome-capsulated curcumin. Journal of
fundamentals to recent developments. Oxford: Trafford Pub. Ltd. Agricultural and Food Chemistry, 57, 9141e9146.
Mourtzinos, I., Salta, F., Yannakopoulou, K., Chiou, A., & Karathanos, V. T. Tommasini, S., Calabrò, M. L., Stancanelli, R., Donato, P., Costa, C.,
(2007). Encapsulation of olive leaf extract in becyclodextrin. Journal Catania, S., et al. (2005). The inclusion complexes of hesperetin
of Agricultural and Food Chemistry, 55, 8088e8094. and its 7-rhamnoglucoside with (2-hydroxypropyl)-b-cyclodextrin.
Nakajima, M., Nabetani, H., Ichikawa, S., & Xu, Q.Y. (2003). Func- Journal of Pharmaceutical and Biomedical Analysis, 39, 572e580.
tional emulsions. US Patent, US6538019B1. Tomren, M. A., Masson, M., Loftsson, T., & Tonnesen, H. H. (2007).
Oetjen, G.-W., & Haseley, P. (2004). Freeze-drying. Weinheim: Wiley- Studies on curcumin and curcuminoids XXXI. Symmetric and
VCH Verlag Gmbh & Co. KGaA. asymmetric curcuminoids: stability, activity and complexation
Pagington, J. S. (1986). a-Cyclodextrin and its uses in the flavour in- with cyclodextrin. International Journal of Pharmaceutics, 338,
dustry. In G. G. Birch, & M. G. Lindley (Eds.), Developments in 27e34.
food flavours. London: Elsevier Applied Science. Tonnesen, H. H., Masson, M., & Loftsson, T. (2002). Studies of cur-
Peter, S., & Given Jr., (2009). Encapsulation of flavors in emulsions for cumin and curcuminoids. XXVII. Cyclodextrin complexation: sol-
beverages. Current Opinion in Colloid & Interface Science, 14, ubility, chemical and photochemical stability. International Journal
43e47. of Pharmaceutics, 244, 127e135.
Z. Fang, B. Bhandari / Trends in Food Science & Technology 21 (2010) 510e523 523
Vaikousi, H., Biliaderis, C. G., & Izydorczyk, M. S. (2004). Solution flow antioxidant effects of quercetin nanoparticles. International Journal
behavior and gelling properties of water-soluble barley (1/3, 1/4)- of Pharmaceutics, 346, 160e168.
b-glucans varying in molecular size. Cereal Science, 39, 119e137. Xiong, S., Melton, L. D., Easteal, A., & Siew, D. (2006). Stability and
van der Graaf, S., Schroen, C. G. P. H., & Boom, R. M. (2005). Prep- antioxidant activity of black currant anthocyanins in solution and
aration of double emulsions by membrane emulsificationea encapsulated in glucan gel. Journal of Agricultural and Food
review. Journal of Membrane Science, 251, 7e15. Chemistry, 54, 6201e6208.
Vilstrup, P. (2001). Microencapsulation of food ingredients. Surrey: Yu, H., & Huang, Q. (2010). Enhanced in vitro anti-cancer activity of
Leatherhead Pub. curcumin encapsulated in hydrophobically modified starch. Food
Watwe, R., & Bellare, J. (1995). Manufacture of liposomes: a review. Chemistry, 119, 669e674.
Current Science, 68, 715e724. Zhang, L., Mou, D., & Du, Y. (2007). Procyanidins: extraction and
Wu, T.-H., Yen, F.-L., Lin, L.-T., Tsai, T.-R., Lin, C.-C., & Cham, T.-M. micro-encapsulation. Journal of Agricultural and Food Chemistry,
(2008). Preparation, physicochemical characterization, and 87, 2192e2197.