128 JOURNAL OF COSMETIC SCIENCE water within the SC may result in lacunar domains, as observed by Menon and Elias (10), losing structural continuity, partially or completely, within the extracellular lipid bi­ layers of the SC. \V/ e suggest that a partial loss in the structural continuity of lacunar domains is responsible for a reduction in the radius of the corresponding aqueous pores, while a complete loss in continuity of lacunar domains is responsible for the elimination or closing of the corresponding aqueous pores, that is, for a reduction in the overall number density of the aqueous pores in the SC. Figure 7 illustrates schematically a combination of lacunae that are continuous under normal skin hydration conditions, resulting in an aqueous pore, but may become discontinuous upon exposure of the skin to glycerol, thereby resulting in a size reduction, or a closing, of the aqueous pore. A second scenario describing how glycerol may result in partial, or complete, loss of the structural continuity of lacunar domains considers the ability of glycerol to maintain the intercellular lipid mortar in a liquid crystalline state, as opposed to a solid crystalline state (30). Froebe et al. have shown that addition of 10 wt% glycerol to a mixture of SC lipids in vitro inhibited the transition from liquid to solid crystals, which could maintain the intercellular lipid mortar in the SC and potentially minimize the size, as well as the continuity, of the lacunar domains within the SC (30). Most likely, we suggest that both scenarios may play a role in inducing partial, and/or complete, loss of structural conri- Aqueous Pore Radius Hydrated Skin Exposing Hydrated Skin to Glycerol Lacunar Domains with No Water Mobility Partial Elimination of Lacunar Structural Continuity - Smaller Aqueous Pore Complete Elimination of Lacunar Structural Continuity - Closed Aqueous Pore Figure 7. Schematic illustration of possible structural modes of interaction of aqueous lacunar domains in the hydrated skin barrier with glycerol. Aqueous lacunar domains, shown in grey, gain structural continuity in hydrated skin to form an aqueous pore. However, when glycerol is added to the hydrated skin barrier, lacunar domains, shown in black, lose structural continuity due to glycerol binding water and minimizing water mobility, either partially, resulting in a smaller aqueous pore, or completely, resulting in a closed aqueous pore.

SDS MICELLES IN SKIN BARRIER PERTURBATION 129 nuity of the lacunar domains, thereby resulting in a reduction in the radius, and/or in the number density of the aqueous pores in the SC. On the other hand, in vitro as well as in vivo studies document that surfactants like SDS have an opposite effect on the SC lipids and on the corneocyte keratins. SDS has been shown to induce direct alteration to the structure of the intercellular lipid mortar (48,49), as well as to disrupt the keratin structure of the corneocytes in the SC (16,50,51). Both of these effects can induce the formation of additional lacunar domains, as well as enhance the structural continuity of existing lacunar domains. This is how SDS may induce an increase in the radius, and/or in the number density, of the aqueous pores in the SC. A mixture of SDS and glycerol in an aqueous contacting solution will result in: (a) glycerol reducing and (b) SDS increasing the radius and the number density of the aqueous pores in the SC. These considerations may help rationalize how adding 10 wt% glycerol to an SDS aqueous contacting solution can reduce the radius and the number density of the aqueous pores induced by SDS in the SC. CONCLUSIONS According to a well-accepted view in the cosmetics literature, surfactant micelles cannot penetrate into the skin due to size limitations, and as a result, surfactant-induced skin barrier perturbation should be determined solely by the concentration of the surfactant monomers (11-23). Moore et al. (11) have recently shown that this is not the case for a model skin irritant, the surfactant SDS. Instead, they hypothesized that SDS micelles can penetrate into the skin barrier and induce skin barrier perturbation. In this paper, for the first time, using mannitol transdermal permeability and average skin electrical resistiv­ ity measurements in the context of a hindered-transport aqueous porous pathway model, we have demonstrated in vitro that SDS induces an increase in the average radius of the skin aqueous pores, from 20 ± 3.A to 33 ± 5.A, such that the SDS micelles of size 19.5 ± 1.A can penetrate into the SC through these aqueous pores. In addition, SDS induces a sevenfold increase in the number density of these aqueous pores, thereby significantly enhancing the SDS micellar contribution to SDS skin penetration and to skin barrier perturbation in vitro. Using in vitro skin radioactivity measurements, we demonstrated that adding 10 wt% glycerol to an aqueous SDS micellar contacting solution significantly reduces: (i) the total extent of SDS skin penetration and (ii) the SDS micelle contribution to SDS skin penetration. This is due to the fact that glycerol eliminates almost completely the contribution of the SDS micelles to SDS skin penetration. Through dynamic light­ scattering measurements, we have verified that glycerol does not increase the size of the SDS micelles, which if increased, could have minimized the SDS micellar contribution to SDS skin penetration. In addition, through surface tension measurements that were used to determine the CMC values of SDS in water and in a 10 wt% glycerol aqueous solution, we have shown that glycerol does not reduce the concentration of the SDS monomers contacting the skin, which if reduced, could have minimized the SDS mo­ nomeric contribution to SDS skin penetration. Using in vitro transdermal permeability and average skin electrical resistivity measurements upon exposure of tllP kin to ;::i]nFous contacting solutions of SDS and of SDS + 10 wt% added glycerol, in the context of a hindered-transport aqueous porous pathway model, we have conclusively demonstrated