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[LITERATURE REVIEW

]

Dimethyl Sulfoxide
History, Chemistry, and Clinical Utility in Dermatology
a
KARA CAPRIOTTI, MD; bJOSEPH A. CAPRIOTTI, MD
a
Bryn Mawr Skin and Cancer Institute, Rosemont, Pennsylvania; bOcean Ophthalmology Group, North Miami Beach, Florida

ABSTRACT
Dimethyl sulfoxide is a colorless liquid derived as a by-product from wood pulp in the production of paper. This colorless
liquid found immediate application as a polar, aprotic solvent miscible with water and able to dissolve an enormous catalog
of polar and nonpolar small molecules. It is presently scarcely used in dermatology, but given its useful properties as a
penetration-enhancing solvent excipient and active anti-inflammatory pharmaceutical agent, dimethyl sulfoxide has the
potential to be used in a much broader capacity. The authors review the history, chemistry, and clinical utility of dimethyl
sulfoxide as it pertains to dermatology. (J Clin Aesthet Dermatol. 2012;5(9):24–26.)

T
opical agents have long been employed for surface mid-to-late 19th century. In the search for cheaper, more
therapies in dermatology. In addition to the diagnostic efficient methods to produce paper from wood pulp, a
advantage afforded by visual signs present on readily process was developed in which its by-products included a
accessible surfaces, in many cases, treatment can be directly variety of sulfide-containing compounds. These malodorous
applied to pathological lesions. The development of neat drug sulfides were converted to less-noxious sulfoxides, including
substances working only on the surface is trivial; no need to DMSO. This colorless liquid found immediate application as
penetrate any physiological barriers, solubilize in carrier a polar, aprotic solvent miscible with water and able to
vehicles, or stabilize in specialized chemical mixtures. A step dissolve an enormous catalog of polar and nonpolar small
up from these most primitive therapies are the simple molecules. Since the 1860s, DMSO has been extensively
solutions, suspensions, and creams placed directly on affected studied in the chemical literature. It is a preferred solvent
areas that need only provide suitable surface delivery for the for a host of named reactions and benefits from both hard
active agent. An armamentarium of novel formulation and soft nucleophile properties. It is routinely used as a mild
techniques has evolved for the treatment of deeper lesions or oxidant in a variety of synthetic schemes and has gained
for the delivery of therapeutic agents that cannot be easily great utility for the study of carbanion chemistry. Aside from
applied as rudimentary preparations. The authors discuss the this novel reaction chemistry, DMSO was soon recognized to
history, chemistry, and clinical utility of one such agent— have the very unique ability to “carry” small molecules
dimethyl sulfoxide (DMSO)—a common, controversial through a variety of barriers. It was noted that DMSO spilled
substance with a storied past. Its use in dermatology is now onto the hands would quickly cause a distinctive garlic taste
limited. It is most commonly used as a keratolytic agent in on the tongue, which led to the systematic investigation of
conjunction with potassium hydroxide (KOH) to enhance DMSO as a transport agent that could be used to deliver
visualization of fungal hyphae when ascertaining the presence small molecules through skin and mucosa.1
of dermatophyte infection. However, DMSO has the potential
for much broader applications. EARLY CLINICAL USE OF DIMETHYL SULFOXIDE
The medical uses of DMSO have generally fallen in to
HISTORY AND CHEMISTRY three functional categories encompassing tissue/organ
Like so many modern medicinal products, DMSO traces preservation, penetration-enhancing solvent excipients, and
its roots to the nascent German chemical industry of the active pharmaceutical agents, primarily anti-inflammatory.

DISCLOSURE: The authors report no relevant conflicts of interest.
ADDRESS CORRESPONDENCE TO: Kara Capriotti, MD, 919 Conestoga Road, Building 2, Suite 106, Rosemont, PA 19010;
E-mail: karacapriotti@gmail.com

24 [September 2012 • Volume 5 • Number 9] 24

Christensen et al6 studied the skin.200 publications on the corneum by disruption of the barrier function. delivering a higher concentration to the membrane approved by the FDA originally in the 1970s and currently barrier. and prompted a flurry of activity assessing effectiveness for curettage for 60 patients with basal cell carcinoma. At 72 different dermatological conditions with mixed results months. Other than the generic extract solute from vehicle.2 The agents. such as rubor. DMSO was found to be dramatically affect one or more of these variables without causing effective for healing severe skin necrosis caused by permanent structural or chemical modification of the accidental extravasation of the anticancer drug mitomycin C physiological barrier.5 sold under a range of brands including Domoso. Domoso Gel. This merits of DMSO. Applying DMSO cream during early stages of CHEMISTRY AND MECHANISM OF PENETRATION pressure ulcers leads to a decrease in pressure ulcer AND TRANSPORT EFFECT occurrence among high-risk patients. DMSO may also play a FDA finally approved a 50% DMSO solution for intravesicular role in partitioning as well by forming solvent administration under the brand name Rimso-50 microenvironments within the tissue that can effectively (NDA#017788) for interstitial cystitis. and Synotoc Otic. 57. The effects reported principal variables that influence penetration of a solute were beneficial. There are more than 1. including DMSO. Finally. were also noted in scleroderma patients. Penetration agents are designed to In the same vein. The (confirmed by histopathology) with favorable cosmetic focus in most of these earlier studies was the results. to say the least. RECENT CLINICAL STUDIES WITH DIMETHYL SULFOXIDE Jacob2 discovered (in fact rediscovered. There is some evidence to suggest that been extensively reviewed in both the scientific and popular DMSO can increase diffusion through the stratum literature. both subjectively and additional similar study evaluated the long-term follow up objectively. and 4) the thickness of the tumor.6 An informative addition to this study would be a demonstration of anti-inflammatory properties delivered similar arm without the use of DMSO in order to assess locally rather than systemically. An showed potential promise. The through any given membrane: 1) the diffusion coefficient most frequent outcome measures were reduction of through the membrane.9 membrane barrier. the permeable packing arrangement. This aminolevulinic acid (5-ALA).4 Systematic investigations of small to carry the 5-ALA further into the dermis in the hopes of molecule transport through the skin with DMSO as a being able to effectively treat nonmelanoma skin cancers carrier also began in the early 1960s as the potential for with less invasive means. an observation he first made in a series of nine effectiveness of photodynamic therapy with 5- patients treated for dermatitis using topical DMSO. 2) the concentration of the agent erythema and rapid healing of ulcers. along with decreased in the vehicle. as it was Current use of DMSO in dermatology is quite limited. There are a variety of veterinary DMSO variety of vehicles. suggesting clinical utility in conditions and diseases clear. 3) the partition coefficient between the signs of inflammation.7 percent of Bowen’s disease and 63. Keloids and At 60 months.8 A systematic review The delivery of any active substance from the surface performed by Duimel-Peeters et al9 looked at the efficacy through to the deeper layers of the skin is governed by the of topical DMSO on wound healing of decubitus ulcers and barrier function of the stratum corneum. both alone and in combination with steroids. dolor. Dramatic healing of ischemic ulcers of for 19 cases of Bowen’s disease and 15 cases of basal cell fingertips was achieved with topical application several carcinoma using topical 5-ALA plus DMSO and times daily over several weeks. but it fell out of favor in the 1960s after the probably occurs through aprotic interactions with United States Food and Drug Administration (FDA) became intercellular lipids and may also include reversible much more rigid following the discovery of limb defects in distortion of lipid head groups that produce a more children born from mothers taking thalidomide.7 DMSO. Cutaneous scleroderma clearance rates without a penetration enhancer.Organ preservation studies by Dr. calor. both for wound healing and analgesia. and has principals 1 to 3. There are four its use as an anti-inflammatory drug. this novel effect began to emerge. DMSO can have a version approved in 2002. and membrane and the vehicle. dimethylsulfoxide. with its unique solvent abilities. is being used affecting the dermis. already known in the German chemical literature as Enhanced penetration of known ingredients is the focus in described above) that DMSO effectively penetrates the which it is being used. this remains the only approved profound solubilizing effect on less soluble agents in a human indication. In 1978. so most penetration by his own lab and a host of other research groups.5 Wound healing is another potential area of interest for use of DMSO. Alteration of membrane thickness is during intravenous administration. increasing penetration simply by preparations.3 Increased skin flexibility ethylenediaminetetraacetic acid (EDTA) with a single and decreased pain resulting in greater range of motion exposure to 630nm diode laser at differing energy dosages. Stanley Jacob in the early nontoxic agents that could reversibly decrease the 1960s led to subsequent pharmacotherapeutic investigations thickness of the stratum corneum). 81 percent of patients remained disease free arising from incompletely understood mechanisms.10 A combination of 10% less practical for drug delivery (it is difficult to conceive of alpha-tocopherole acetate and 90% DMSO applied topically [ September 2012 • Volume 5 • Number 9] 25 . attempt to reversibly alter therapeutic history is controversial.3 hypertrophic scars showed flattening after several months percent of basal cell carcinomas remained histologically of use. Synsac.

SUMMARY 7. Ann NY Acad Sci. Wagner EK.59(11):1318–1319. inhibits viral deoxyribonucleic acid (DNA) 5. transport into the local blood vessels. surprising results were found. Stoughton RB. 1966. Kitzmiller K. Investigative studies with Sciences. Cleveland Clin Quart.33:41–43. as demonstrated with 10. Fritsch W. et al. Hornito. Bischel M. Prevention of absorption when compared to DMSO alone or 5-FU alone in cytotoxic drug induced skin ulcers with dimethyl sulfoxide cream bases. 26 [September 2012 • Volume 5 • Number 9] 26 . 2009. after extravasation into tissue of 2. Case report: topical DMSO for mitomycin-C increased penetration of 5-fluorouracil (5-FU) in the induced skin ulceration. A. infectivity. McCormack LJ.141(1):428–436. J Eur Acad Dermatol Venereol. Curr Ther Res Clin Exp. 2003. tingling or burning. Souza CS. Herschler RJ. Obrist R. triggers sulfoxide on wound healing and as an anti-inflammatory drug. dermatology. Poppo MJ. DMSO reduces virion South Med J. Treatment of diabetic and garlic odor from the breath.prophylactically. Dimethyl sulfoxide (DMSO) in clinical dermatology.18(4): treatment of superficial malignancies and warts. 1965. Roy D. The reason is not entirely clear because its single session for non-melanoma skin cancer. Engel MF.23(3):327–329. et al.32:47–56. Dimethyl sulfoxide (DMSO): antineoplastic agents but before ulceration. Alteration of collagen in Of interest. 12. DMSO review of the efficacy of topical skin application of dimethyl facilitates diffusion through the stratum corneum. Duimel-Peeters. LJ Weber. Viset T. Dimethyl sulfoxide blocks herpes simplex virus-1 productive infection in vitro acting at REFERENCES different stages with positive cooperatively. Halfens RJ. dermatology for DMSO lies in its ability to act as an effective J Am Geriatric Soc. and reduces the transcripts level of many HSV-1 on human percutaneous absorption. BMC Infectious 1. Christensen E. Ferreira J. dissolved in dimethyl sulfoxide (DMSO) and other vehicles. 2009. Ludwig CU. rarely causing occasional side Photodyn Ther. 8. Snoeckx LH.23(1):58–66. vehicle. 2002. generalized scleroderma after treatment with dimethylsulfoxide: In a study looking at the effect of DMSO on several preliminary report.2(9):1–10. Eur J Cancer Clin Oncol.15(11):361–370. effects. and promotes Wounds. A systematic used in combination with other substances. Stoll HR. Photodiagnosis application is not dangerous. Kadar I. has been found a new concept in pharmacotherapy. Lasher M. Dorr RT. Arch Derm. These findings suggest that the DMSO itself may have 6. DMSO may have some antiviral effects as well. diverging from previous Photodynamic therapy with 5-aminolaevulinic acid. the formation of deposits in the dermis. 1985. Lang R. Oncol Nurs Forum.6(3–4):207–213. breakdown. Topical 693–695. Raved M. Skogvoll E. et al.11 3. Jacob SW.3:1389.90:512. Felicio LV. It greatly enhances percutaneous penetration when 9. Obrecht JP. itself to numerous applications for other future products in 1987. skin irritation. 1964. DMSO in dermatology. Igelman JM. Skin penetrating property of drugs Diseases. Life 13. a role in antiherpetic activity. Goldman L. 1991. application of DMSO with 5-FU demonstrated superior 11.13 This unique penetrating ability may lend (DMSO) and alpha-tocopherole. thought that it only functioned as a penetrant for antiviral dimethylsulfoxide and curettage in basal cell carcinoma: a 6-year medications.12 clinical and histological follow-up. Aguilar JS. to universally prevent severe ulceration and tissue 1964. Influence of dimethylsulfoxide( DMSO) replication. Alberts D. 1964. parameters of herpes simplex virus (HSV) replication. such as itching. some 4.6:134–135. Long-term follow-up of Dermatological studies with DMSO in humans have been topical 5-aminolaevulinic acid photodynamic therapy diode laser scarce. The most definitive role in perforating ulcers (mal perforate) with local dimethyl sulfoxide. genes. Waroe T. 1967. Scherbel AL. Sundstrom S.