Lag time data for characterizing the pore pathway of intact and chemically pretreated human epidermal membrane

Abstract This study aimed to gain mechanistic insights into the nature of the pore pathway of fully hydrated human stratum corneum from lag time data obtained using a model polar permeant, urea. Lag times were deduced from transport experiments with human epidermal membranes and with human epidermal membranes after ethanol or chloroform–methanol treatment. A tortuous pore pathway transport model and a `bottleneck' transport model were employed for data analysis, and their appropriateness for the observed data was examined. Important outcomes from the present study with intact and with delipidized stratum corneum were as follows. Long lag times (around 60–800 min) for the transport of urea in human epidermal membranes were generally observed. These results were consistent with an extremely tortuous pore pathway as would be expected if it is associated with the polar/aqueous region of the stratum corneum intercellular lipids (i.e. the bilayers in the intercellular region). The permeability of the stratum corneum increased after ethanol treatment, and, at the same time, the tortuosity decreased but remained relatively high. Chloroform–methanol treatment further increased the permeability and further decreased the tortuosity. Since delipidization by ethanol and chloroform–methanol treatments decreased the tortuosity of the pore pathway, these results suggest that the effectively highly tortuous pathway for polar permeants in stratum corneum may be associated with the polar regions of the intercellular lipids. Untreated skin samples that had high electrical resistance were observed to have longer lag times than those with low resistance; this is consistent with the hypothesis that skin samples of high resistance have less appendage routes or less damage and transport polar permeants predominantly via the tortuous pathways involving the intercellular lipid regions of the stratum corneum. Neither the tortuous pathway transport model alone nor the `bottleneck' transport model alone seems to perfectly represent the experimental data, and a modified model (a hybrid of the two models) has been proposed to be more consistent with the lag time data and the morphology of fully hydrated stratum corneum. The present study has demonstrated the usefulness of lag times obtained with a polar permeant in better understanding the transport mechanisms involved with the pore pathway.