124 JOURNAL OF COSMETIC SCIENCE that a free SDS micelle, being smaller than the aqueous pore, is able to penetrate into the SC, while a PEO-bound SDS micelle, being larger then the aqueous pore, is not able to do so. Our hypothesis to explain the observed dose-dependence of SDS skin penetra­ tion in the absence of glycerol is similar to that of Moore et al. (11), the difference being that we have further substantiated this hypothesis by directly determining the average skin aqueous pore radius, r pore ' and the pore number density, e!T, of the skin aqueous pores induced by SDS. Considering the skin penetration of both the SDS monomers and the SDS micelles, we have investigated in vitro the following three hypotheses to explain the ability of glycerol to minimize the contribution of SDS micelles to SDS skin penetration: (i) the addition of 10 wt% glycerol to the SDS aqueous contacting solution reduces the concentration of the SDS monomers contacting the skin, and/or (ii) the addition of 10 wt% glycerol to the SDS aqueous contacting solution increases the SDS micelle size relative to that of the skin aqueous pores, such that the larger SDS micelles can no longer penetrate through these aqueous pores into the SC, and/or (iii) the addition of 10 wt% glycerol to the SDS aqueous contacting solution reduces the radius, r p o r e • and the number density, e/'T, of the skin aqueous pores, such that the SDS micelles, which are on average larger than the skin aqueous pores, can no longer penetrate into the SC and contribute to SDS skin pen­ etration. According to hypothesis (iii), in addition to the decrease in the radius of the aqueous pores, the decrease in the number density of the aqueous pores should further limit the ability of the SDS micelles to penetrate into the SC through these aqueous pores. We have investigated hypothesis (i) by conducting surface tension measurements to deduce the CMC of SDS in aqueous solution in the absence and in the presence of 10 wt% glycerol. Hypothesis (ii) was investigated through DLS measurements to determine the SDS micelle hydrodynamic radius in aqueous solution in the absence and in the presence of 10 wt% glycerol. Finally, we investigated hypothesis (iii), by determining the radius and the number density of the skin aqueous pores induced by aqueous SDS contacting solutions in the absence and in the presence of 10 wt% glycerol through our average skin electrical resistivity and mannitol transdermal permeability measurements, in the context of the hindered-transport porous aqueous pathway model. We discuss the results of studies (i-iii) above in the following three sections. (i) Results from the surface tension measurements to determine the CMC. Recall that the CMC of a SDS aqueous contacting solution is the threshold total SDS concentration above which the concentration of the SDS monomers remains approximately constant, while that of the SDS micelles continues to increase upon increasing the total SDS concen­ tration. Therefore, if the addition of 10 wt% glycerol to the SDS aqueous contacting solution results in a lowering of the CMC, one may conclude that the number of SDS monomers contacting the skin decreases in the presence of glycerol, which may explain why glycerol reduces SDS skin penetration. However, our surface tension results indicate that the CMC of SDS in the presence of 10 wt% glycerol is 9.2 mM, which is slightly larger than the CMC of SDS in the absence of glycerol (8.7 mM). Our CMC value in (continued) penetration, formed the basis for their hypothesis that SDS micelles can penetrate into the SC, based on a size limitation. However, Moore et al. did not measure the effect of SDS on the radius and on the number density of the skin aqueous pores directly, as is done here.

SDS MICELLES IN SKIN BARRIER PERTURBATION 125 the presence of glycerol is in excellent agreement with previously reported CMC values of SDS in water/glycerol binary mixtures (46). Therefore, based on the CMC values of SDS in water and in a 10 wt% glycerol aqueous solution, one may conclude that hypothesis (i) is not valid, and therefore, cannot explain the observed ability of glycerol to reduce SDS skin penetration. (ii) Results from the dynamic light-scattering (DLS) measurements to determine the size of the SDS micelles. Using DLS, we determined the sizes of the SDS micelles in aqueous solutions, in the absence and in the presence of 10 wt% glycerol. Figure 5 shows the results of the DLS measurements in terms of the SDS micelle hydrodynamic radii in: (a) water and (b) 10 wt% glycerol aqueous solutions. The SDS micelle hydrodynamic radii were deter­ mined by extrapolation to a zero micelle concentration, which corresponds to the CMCs of SDS solutions corresponding to (a), 8.7 mM (see the diamonds in Figure 5), and to (b), 9.2 mM (see the triangles in Figure 5). Using a linear regression analysis, we determined that the hydrodynamic radius of the free SDS micelles corresponding to (a) is 19.5 ± 1 A, while that corresponding to (b) is 18.5 ± 1 A. The SDS micelle hydro­ dynamic radii corresponding to (a) reported here are in excellent agreement with the values reported previously by Moore et al. (11) and by Almgren and Swamp (47). Therefore, these results indicate that the SDS micelle size is slightly smaller, not larger, in the SDS aqueous solution with 10 wt% added glycerol, and hence, cannot explain how glycerol minimizes the SDS micellar contribution to SDS skin penetration. In other words, hypothesis (ii) is not valid either. (iii) Results from an analysis of the hindered-transport aqueous porous pathway model to determine the radius and the number density of the skin aqueous pores. We quantified the extent of skin barrier perturbation using the average aqueous pore radius and the pore number density as quantitative descriptors of the SC morphological changes upon exposure to: (a) an 20 € 19.5 +----------r--------- ➔ ----------t 19 ·e ! 18.5 , "C "C 18 , -� 17.5 in in 17 16.5 0 10 15 20 25 30 35 Concentration of SDS Micelles (mM) Figure 5. Measured effective radii of SDS micelles in aqueous solutions in the absence (diamonds) and in the presence (triangles) of 10 wt% glycerol plotted versus the SDS concentration minus the CMC, which corres1-1onJs to the concentrat.i.on of the SDS m.i.celles, us.i.ng DLS nieasurements at 25 ° C. The SDS micelle radii were determined using a CONTIN analysis. The error bars reflect standard errors based on six samples at each SDS concentration.