Evaluation of solute permeation through the stratum corneum: Lateral bilayer diffusion as the primary transport mechanism

Solute permeation across human stratum corneum (SC) was examined in terms of the fundamental bilayer transport properties. A mathematical model was developed to describe the macroscopic SC permeation via the interkeratinocyte lipid domain in terms of (i) the structure and dimensions of the SC, and (ii) the microscale lipid bilayer transport properties, which include the bilayer/water partition coefficient, the lateral diffusion coefficient, the interfacial transbilayer mass transfer coefficient, and the intramembrane transbilayer mass transfer coefficient. The relative importance of the diffusive resistances associated with the bilayer transport properties was evaluated with the model and experimental data. Lateral diffusion coefficients in SC lipid bilayers were calculated from 120 human skin permeability measurements, and compared with previously reported measurements made in SC-extracted lipids. Good qualitative and quantitative agreement was observed, indicating that, in the context of the model, the diffusive resistance associated with lateral diffusion is sufficient to explain the overall resistance of solute permeation through the SC. A similar analysis shows that the diffusive resistance associated with interfacial transbilayer transport is not capable of explaining the experimental permeation values, thus supporting this finding. The lateral diffusion analysis also revealed a bifunctional size dependence of transport within the SC, with a strong size dependence for small solutes (<300 Da) and a weak size dependence for larger solutes.