J. Soc. Cosmet Chore., 21,853-873 (Dec. 9, 1970) Effects of Surfactants and Solvents on the Permeability of Epidermis ROBERT SCHEUPLEIN, Ph.D., and LISA ROSS, A.B.* Presented December 2, 1969, New Yorh City Synopsis--The PERMEABILITY of the skin is increased after or during contact with a variety of substances. Many of these substances do not cause great permanent damage to the skin and, in some cases, the transport properties of the stratmn corneum are only temporarily altered. Within this category of substances are: (a) some LIPID SOLVENTS (b) WATER and other hydrogen-bonded liquids and (c) SOAPS and DETERGENTS. Representatives of these three classes of materials have been tested for their initial and lasting effect on the permeability of human EPIDERMIS in vitro. The permeability of tritiated water was used as a criterion of damage. Lag times for diffusion, activation ener- gies, and "botmd water" measurements of variously treated membranes arc reported. The data suggest that the mechanism of action of each of the three classes of substances is dif- ferent. A mechanism accounting for the damage produced and for the resulting enhanced diffusion is proposed in each case. INTRODUCTION There are many substances which, when applied to the skin, can alter its appearance, suppleness, and permeability--properties which de- pend to a large extent on the state of the stratum comeurn. Of major interest are those substances which have a mild effect or even a reversible effect on the tissue. For with these substances it may be possible to temporarily alter the properties of the skin to our advantage. There- fore, excluded from consideration are strongly corrosive chemicals like concentrated alkali, certain concentrated acids, etc., which permanently damage the skin. * Department of Dermatology, Harvard Medical School at the Massachusetts General Hos- pital, Fruit Street, Boston, Mass. 02114. 853

854 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS It is known, for example, that the permeability of the skin is in- creased after treatment with any one of several nonpolar solvents (1). Such treatment removes more or less of the lipids from the stratum corneum (the skin's major rate limiting permeability barrier) and radically increases its permeability. Significantly, the barrier function is substantially, if not completely, restored if these lipids are reincorpo- rated into the tissue but otherwise the damage is permanent (2). The role of the skin lipids is complex we know that they do not simply form a protective barrier film on the surface of the skin. But apart from recognizing that in some way the lipids are essential to the in- tegrity of the tissue as a whole, we know little else about their role. Other solvents appear to be capable of increasing the permeability of the horny layer without necessarily extracting lipids. Perhaps the most important example is water (3). Hydration can increase the permeability of the skin by as much as eightfold. The well-hydrated horny layer is nonetheless a stable and extremely effective diffusion barrier in comparison with the viable skin layers. Other polar sol- vents, e.g., dimethyl sulfoxide (DMSO) and dimethylformamide (DMFA), are also effective vehicles for increasing skin penetration (4). The en- hancement of permeability arises from an increase in the diffusivity of the stratum corneum in the presence of the solvent. DMSO does not act as a "carrier" nor is the increased permeability due simply to a more favorable partition coefficient for the particular solute (5). It has been reported that the effects of DMSO are to a substantial degree reversible in that the permeability of the tissue is largely restored after the DMSO is removed (4). But this point is still in dispute (6). In the cases cited above, the particular substance was presented as the pure solvent, hence in large concentration, and not as the minor constituent of a dilute solution. Dilute solutions (0.1-0.5M) of DMSO, DMFA, and lipid solvents like ethanol or butanol have no appreciable effect on the permeability of the tissue. In contrast, anionic detergents and soaps are effective in dilute solution. One per cent aqueous solutions of "Teepol," a secondary alkyl sulfate, and potassium palmitate were both found to increase the permeability of water through human epi- dermis (7). The effect of these anionic surfactants is also reported to be reversible the tissue's permeability to water returns to normal when the surfactants are removed. The observations described above are intriguing in that they sug- gest ways in which the skin might temporarily be made more permeable