A geometrical model for diffusion of hydrophilic compounds in human stratum corneum

A three-dimensional diffusion model with either hexagonal or cylindrical symmetry has been constructed to simulate desorption profiles of hydrophilic chemicals from the topmost layer of human skin (the stratum corneum) as measured in ex vivo studies. The tissue is pierced by skin appendages - sweat glands and hair follicles - which in this particular scenario are considered to be perfect sinks. Desorption profiles of nine test permeants covering a wide range of lipophilicity were analyzed. By optimizing transverse and lateral diffusion coefficients to match these profiles, it was found that the lateral diffusivity values exceeded the transverse values by average factors ranging from 45 (hexagon model) to 71 (cylinder model). However, transverse clearance exceeded lateral clearance by factors ranging from 8 to 27 (cylinder model); these values were strongly influenced by the thickness of the individual tissue samples, as expected. The results confirm the validity of earlier estimates of transverse diffusivity of hydrophilic compounds in human stratum corneum based on purely one-dimensional models. They furthermore confirm that transcellular transport is an important component of the stratum corneum's polar pathway, in addition to the already-recognized appendageal transport mechanism.