J. Cosmet. Sci., 58, 109-133 (March/April 2007) The role of sodium dodecyl sulfate (SDS) micelles in inducing skin barrier perturbation in the presence of glycerol SASWATA GHOSH and DANIEL BLANKSCHTEIN, Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139. Accepted for Publication November 29, 2006. Synopsis The stratum corneum (SC) serves as the skin barrier between the body and the environment. When the skin is contacted with an aqueous solution of the surfactant sodium dodecyl sulfate (SDS), a well-known model skin irritant, SDS penetrates into the skin and disrupts this barrier. It is well established, both in vitro and in vivo, that the SDS skin penetration is dose-dependent, and that it increases with an increase in the total SDS concentration above the critical micelle concentration (CMC) of SDS. However, when we added the humectant glycerol at a concentration of 10 wt% to the aqueous SDS contacting solution, we observed, through in vitro quantitative skin radioactivity assays using 14 C-radiolabeled SDS, that the dose dependence in SDS skin penetration is almost completely eliminated. To rationalize this important observation, which may also be related to the well-known beneficial effects of glycerol on skin barrier perturbation in vivo, we hypothesize that the addition of 10 wt% glycerol may hinder the ability of the SDS micelles to penetrate into the skin barrier through aqueous pores that exist in the SC. To test this hypothesis, we conducted mannitol skin permeability as well as average skin electrical resistivity measurements in vitro upon exposure of the skin to an aqueous SDS contacting solution and to an aqueous SDS + 10 wt% glycerol contacting solution in the context of a hindered-transport aqueous porous pathway model of the SC. Our in vitro studies demonstrated that the addition of 10 wt% glycerol: (i) reduces the average aqueous pore radius resulting from exposure of the skin to the aqueous SDS contacting solution from 33 ± 5 A to 20 ± 5 A, such that a SDS micelle of radius 18.5 ± 1 A (as determined using dynamic light-scattering measurements) experiences significant steric hindrance and cannot penetrate into the SC, and (ii) reduces the number density of aqueous pores in the SC by more than 50%, thereby further reducing the ability of the SDS micelles to penetrate into the SC and perturb the skin barrier. INTRODUCTION AND SIGNIFICANCE Human skin consists of three stratified layers, the stratum corneum, the viable epider­ mis, and the dermis (1). The stratum corneum (SC), which is the topmost layer of the skin, possesses an ordered brick-and-mortar structure, which consists of the flat corneo- Address all correspondence to Daniel Blankschtein. 109

110 JOURNAL OF COSMETIC SCIENCE cytes (the cellular bricks), interlocked with the lipid lamellae (the intercellular mortar) (2-5). Compared to the porous structure of the viable epidermis and the porous-and­ hydrated structure of the dermis, the rigid and ordered structure of the stratum corneum makes it a very effective permeability barrier that is primarily responsible for the skin barrier function (2--4). The lipid lamellae of the SC consist of lipid bilayers alternating with aqueous, hydrophilic layers (1--4). Under passive skin permeation conditions, per­ meants traverse the SC through diffusion across the lipid lamellae. Although diffusion through the "oily" lipid lamellae can explain the permeation of hydrophobic molecules across the SC, it cannot explain the permeation of hydrophilic molecules across the SC, as observed in many earlier studies (6-9). Indeed, if no aqueous/hydrophilic transport pathways existed within the SC oily lipid domain, then aqueous/hydrophilic permeants, for example mannitol (6-9), could not traverse the SC solely through the lipoidal/hydrophobic pathways that exist in the lipid bilayer domains in the SC. The observation that hydrophilic solutes are able to permeate across the SC, even under passive skin permeation conditions, has led researchers to propose the existence of tortuous, aqueous porous pathways through the intercellular lipid lamellae in the SC. In fact, Menon and Elias (10) have established a morphological basis for the existence of a pore pathway in the mammalian SC. They applied hydrophilic and hydrophobic tracers in vivo to murine skin under passive skin permeation conditions, and also under enhanced skin permeation conditions, using chemical enhancers, a lipid synthesis inhibitor, sonophoresis, and iontophoresis, and following that, they utilized ruthenium tetroxide staining and microwave post fixation methods to visualize the resulting penetration pathways (10). Their results revealed that both the hydrophobic and the hydrophilic tracers localized to discrete lacunar domains embedded within the extracellular lipid lamellar domains (10). Menon and Elias also observed that under skin permeation enhancement conditions, the lacunar domains exhibited an increasing extent of structural continuity when compared to passive skin permeation conditions (10). Hence, structurally continuous lacunar domains have been considered by Menon and Elias as providing a physical basis for the existence of aqueous pores and polar pathways through the intercellular lipoidal mortar in the SC (10). These aqueous pores in the SC provide the primary skin barrier penetration and transport pathways for hydrophilic chemicals, which would otherwise not be able to penetrate into the skin barrier through the lipoidal, hydrophobic pathways that exist in the SC (6-11). In general, surfactants commonly encountered in skin care formulations are known to reduce the barrier properties of the skin (11-15). It is well-accepted that surfactants have to first penetrate into the skin barrier before they can reduce the skin barrier properties. Therefore, if a formulator can minimize surfactant skin penetration, this should also minimize the ability of the surfactant to reduce the skin barrier properties. Sodium dodecyl sulfate (SDS), an anionic surfactant and a model skin irritant, penetrates into and disrupts the skin barrier upon contacting it from an aqueous solution. The SDS mono­ mers self-assemble to form micelles at concentrations above the critical micelle concen­ tration (CMC). Moore et al. (11) and others (12,13) have observed, both in vitro and in vivoJ that the SDS-induced skin barrier disruption is dose-dependent, and that it in­ creases with an increase in the total SDS concentration above the CMC of SDS. This important observation contradicts the well-accepted monomer penetration model (MPM), which attempts to explain surfactant skin penetration by considering solely the role of the surfactant monomers that can penetrate the skin barrier through the aqueous