J. Cosmet. Sci., 54, 143-159 (March/April 2003) Penetration of mixed micelies into the epidermis: Effect of mixing sodium dodecyl sulfate with dodecyl hexa(ethylene oxide) PETER N. MOORE, ANAT SHILOACH, SUDHAKAR PUVVADA, and DANIEL BLANKSCHTEIN, Department of Chemical Enginering, Massachusetts Institute of Technology, Cambridge, MA 02139 (P.N.M., D.B.) and Unilever Home and Personal Care NA, Trumbull, CT 06611 (A.S., S.P.). Accepted for publication November 15, 2002. Synopsis The penetration of the anionic surfactant sodium dodecyl sulfate (SDS) into the epidermis from contacting solutions of SDS and the nonionic surfactant dodecyl hexa(ethylene oxide) (C12E6) was measured for three SDS concentrations (25 raM, 50 raM, and 100 raM) and three SDS solution compositions (1, 0.83, and 0.50). The addition ofC•2E 6 to the SDS solutions was found to decrease the amount of SDS penetrating into the epidermis. The observed decrease occurred via two plausible mechanisms: (i) the addition of C12E 6 decreased the SDS monomer concentration, thus reducing the driving force for the penetration ofmonomeric SDS into the epidermis, and (ii) the addition of C12E 6 reduced, or prevented, the penetration of micellar SDS into the epidermis. Using dynamic light scattering, the hydrodynamic radii of the SDS/%2E6 micelies were determined to be 20 •, for the Otn• = 1 micelies, 24 • for the Otn• = 0.83 micelies, and 27 • for the Otn• = 0.50 micelles (where O•n• denotes the SDS micelle composition). A comparison with typical stratum comeurn aqueous pore radii reported in the literature (10-28 •) suggests that the O•n• = 1 (pure SDS) micelles are able to penetrate into the epidermis, while the o%• = 0.83 and the o• m = 0.50 SDS/C12E 6 mixed micelles are sterically hindered from doing so due to their larger sizes. The observed reduced penetration of SDS into the epidermis upon the addition of Ct2E 6 could lead to a reduction in the skin irritation potential of SDS, provided that there is a relationship between the concentration of SDS in the epidermis and the skin irritation induced by SDS. INTRODUCTION The study of why and how surfactants induce skin irritation and skin damage has broad implications, from the design of mild personal care products to assisting the transport of therapeutic drugs across the stratum corneum (SC) (1-12). Previous studies have compared the irritation potential of different surfactants (3,8,10,11,13-16), and have also determined how different surfactants can lead to changes in the permeability of the Address all correspondence to Daniel Blankschtein. 143

144 JOURNAL OF COSMETIC SCIENCE skin (1,2,9,17-20). Although various mechanisms have been invoked to explain surfac- tant-induced skin irritation, in the majority of these mechanisms the surfactant must penetrate into the skin in order to induce irritation (1,3,7,9,10,19-23). Accordingly, a simple way to reduce the skin irritation potential of a surfactant solution involves reducing the amount of surfactant that penetrates into the skin. A widely accepted view regarding surfactant-induced skin irritation is that, at surfactant concentrations exceeding the critical micelie concentration (CMC), where surfactant micelies first form, only surfactant monomers can penetrate into the skin, either because surfactant micelles are not surface-active or because they are too large to penetrate into the SC (3,6,14,16,18,24,25). This description of surfactant monomer penetration into the skin will be referred to hereafter as the monomer penetration model. The monomer penetration model is based primarily on experimental observations using mixtures of surfactants, where surfactant-induced skin irritation was correlated with the CMC of the surfactant mixtures examined (6,24,26). The surfactant monomer concentration is ap- proximately equal to the CMC (27), and therefore, according to the premise of the monomer penetration model, only the surfactant monomers should contribute to the observed surfactant-induced skin irritation. We have recently challenged the monomer penetration model by unambiguously dem- onstrating that micelles of the anionic surfactant sodium dodecyl sulfate (SDS) contrib- ute significantly to SDS penetration into the epidermis at SDS concentrations exceeding the CMC (28). The fact that SDS micelies were found to contribute to SDS penetration into the epidermis clearly contradicts the monomer penetration model, which predicts that the micellar surfactant should have no effect on surfactant penetration into the epidermis. In addition, we demonstrated that the SDS micelle contribution to skin penetration can be eliminated by mixing SDS with poly(ethylene oxide) (PEO), a non- ionic polymer known to bind to SDS micelies, to form PEO-bound SDS micelies (28). To explain both findings, we proposed a new model of surfactant penetration into the skin, in which the free SDS micelies are sufficiently small to access the aqueous pores of the SC, while the PEO-bound SDS micelles are sterically hindered from doing so due to their larger size. In contrast to the monomer penetration model, the new surfactant skin penetration model highlights the potential importance of the micelles in determining surfactant penetration into the skin. If the miceIlar surfactant is able to penetrate into the skin, then one predicts the commonly reported dose-dependent skin irritation re- sponse to surfactants (2,3,8,13,16,18), as well as providing an explanation for the increased penetration of surfactants into the skin beyond the CMC (25,28,29). The monomer penetration model fails to predict this observed dose dependence because at surfactant concentrations exceeding the CMC, where the concentration of surfactant monomers is constant, there should be no effect of increasing the total surfactant concentration on the surfactant-induced skin irritation. An important question that arose from our previous investigation (28) is whether mixing surfactants will have an effect on the ability of the micellar surfactant to penetrate into the skin. It is well known that mixing surfactants can lower the surfactant monomer concentration (24,30,31). In fact, the relationship observed between the reduction in the surfactant monomer concentration due to mixing surfactants and the resulting skin irritation reduction was used as the basis for the monomer penetration model (6,24,26). However, having demonstrated that the micellar surfactant can contribute to surfactant penetration into the skin (28), it became important to determine whether mixing