Transdermal and lateral effective diffusivities for drug transport in stratum corneum from a microscopic anisotropic diffusion model

This paper presents a computational model of molecular diffusion through the interfollicular stratum corneum. Specifically, it extends an earlier two-dimensional microscopic model for the permeability in two ways: (1) a microporous leakage pathway through the intercellular lipid lamellae allows slow permeation of highly hy-drophilic permeants through the tissue; and (2) the model yields explicit predictions of both lateral (Dsc || ) and transdermal (Dsc & BOTTOM;) effective (average, homogenized) diffusivities of solutes within the tissue. We present here the mathematical framework for the analysis and a comparison of the predictions with experimental data on desorption of both hydrophilic and lipophilic solutes from human stratum corneum in vitro. Diffusion in the lipid lamellae is found to make the effective diffusivity highly anisotropic, with the predicted ratio Dsc || /Dsc & BOTTOM; ranging from 34 to 39 for fully hydrated skin and 150 to more than 1000 for partially hydrated skin. The diffusivities and their ratio are in accord with both experimental data and the results of mathematical analyses performed by others.

Automated summary

This paper presents a computational model that extends an earlier microscopic model for permeability in two ways: allowing slow permeation of hydrophilic substances through the tissue via a microporous leakage pathway, and yielding explicit predictions of diffusivities within the tissue. The model is validated through a comparison of predictions with experimental data, showing good agreement for both hydrophilic and lipophilic solutes in vitro. The model also reveals highly anisotropic effective diffusivity due to diffusion in the lipid lamellae.