LAG TIME DATA FOR CHARACTERIZING THE PORE PATHWAY OF INTACT AND CHEMICALLY PRETREATED HUMAN EPIDERMAL MEMBRANE

This study aimed to gain mechanistic insights into the nature of the p ore pathway of fully hydrated human stratum corneum from lag time data obtained using a model polar permeant, urea. Lag times were deduced f rom transport experiments with human epidermal membranes and with huma n epidermal membranes after ethanol or chloroform-methanol treatment. A tortuous pore pathway transport model and a 'bottleneck' transport m odel were employed for data analysis, and their appropriateness for th e observed data was examined. Important outcomes from the present stud y with intact and with delipidized stratum corneum were as follows. Lo ng lag times (around 60-800 min) for the transport of urea in human ep idermal membranes were generally observed. These results were consiste nt with an extremely tortuous pore pathway as would be expected if it is associated with the polar/aqueous region of the stratum corneum int ercellular 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 relativ ely high. Chloroform-methanol treatment further increased the permeabi lity and further decreased the tortuosity. Since delipidization by eth anol and chloroform-methanol treatments decreased the tortuosity of th e pore pathway, these results suggest that the effectively highly tort uous pathway for polar permeants in stratum corneum may be associated with the polar regions of the intercellular lipids. Untreated skin sam ples 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 ro utes or less damage and transport polar permeants predominantly via th e tortuous pathways involving the intercellular lipid regions of the s tratum corneum. Neither the tortuous pathway transport model alone nor the 'bottleneck' transport model alone seems to perfectly represent t he 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 t he morphology of fully hydrated stratum corneum. The present study has demonstrated the usefulness of lag times obtained with a polar permea nt in better understanding the transport mechanisms involved with the pore pathway. (C) 1998 Elsevier Science B.V. All rights reserved.