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Accurate, predictive computer models for transdermal transport could greatly reduce the need for human and animal testing and elucidate the mechanisms behind observed transport behavior. In this talk, I will focus on 2D microscopic in silico models of the human stratum corneum (SC), which typically represent the SC as corneocytes bricks embedded in a lipid bilayer mortar. Microscopic SC model output is highly dependent on idealized SC geometry, transport pathway (transcellular vs. intercellular), and solute transport parameters (e.g. solute diffusivity in lipids). We have developed a microscopic finite element model (FEM) and employed it for two main purposes: 1) to examine the model output’s sensitivity to a variety of solute transport parameters reported in the literature, variations in geometry, transport pathway, and hydration level, and 2) to examine potential geometric variations that give rise to the differences in transepidermal water loss (TEWL) between infants and adults. Our adult solute transport model results show that model predictions vary widely based on input parameters, with order-of-magnitude differences in lag times and permeabilities for different structure, hydration, and parameter combinations, indicating that experimentally-verified transport parameters and individualized SC structures are necessary for fully predictive models. Our infant and adult TEWL model results indicate that experimentally-observed higher TEWL values in infants as compared to adults is likely caused by fewer corneocyte layers in infant SC as compared to adult SC.
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