A Composite Model for the Transport of Hydrophilic and Lipophilic Compounds Across the Skin: Steady-State Behavior.

A porous pathway feature has been added to an existing skin diffusion model (Dancik et al. 2013. Adv Drug Deliv Rev 65:221-236) in order to extend the range of applicability to highly polar solutes that do not readily diffuse across the stratum corneum lipid/corneocyte matrix. The porous pathway consists of two components: Pathway A is appendageal and is implemented as an array of aqueous shunts (the macropores) which themselves have microporous walls with transient aqueous pores (the micropores). Two varieties of shunts are discussed, one representing a terminal hair follicle, the other an eccrine sweat duct; however, the focus here is on the hair follicle. Pathway B is transcellular, with lipid-phase transport accomplished through defects or breaks in the bilayer lipid structure. The composite model admits polar solutes into the skin in a size-selective manner with an effective micropore radius of 1.6 nm. Steady-state permeabilities, desorption rates from isolated stratum corneum and stratum corneum/water partition coefficients of both polar and lipophilic solutes are effectively explained.