A Microscopic Multiphase Diffusion Model of Viable Epidermis Permeability

A microscopic model of passive transverse mass transport of small solutes in the viable epidermal layer of human skin is formulated on the basis of a hexagonal array of cells (i.e., keratinocytes) bounded by 4-nm-thick, anisotropic lipid bilayers and separated by 1-μm layers of extracellular fluid. Gap junctions and tight junctions with adjustable permeabilities are included to modulate the transport of solutes with low membrane permeabilities. Two keratinocyte aspect ratios are considered to represent basal and spinous cells (longer) and granular cells (more flattened). The diffusion problem is solved in a unit cell using a coordinate system conforming to the hexagonal cross section, and an efficient two-dimensional treatment is applied to describe transport in both the cell membranes and intercellular spaces, given their thinness. Results are presented in terms of an effective diffusion coefficient, D¯epi, and partition coefficient, K¯epi/w, for a homogenized representation of the microtransport problem. Representative calculations are carried out for three small solutes—water, L-glucose, and hydrocortisone—covering a wide range of membrane permeability. The effective transport parameters and their microscopic interpretation can be employed within the context of existing three-layer models of skin transport to provide more realistic estimates of the epidermal concentrations of topically applied solutes.