Modelling the diffusion of xenobiotic compounds in the skin: A review.

Interest for in silico skin xenobiotic absorption models has been growing in the last years owing to the economic advantage of computer simulations over costly experimental procedures. This review presents a classification of the modelling categories reported in the scientific literature so far, discussing their capabilities and limitations. First, Quantitative Structure Permeability Relationships (QSPR) are presented and discussed, followed by Physiologically-Based Pharmacokinetic Models (PBPK). PBPK models include the compartmental approach, and modelling approaches based on the solution of the discretized diffusion equations in geometric representations of the skin in a Computational-Fluid-Dynamics-like manner. The latter modelling category allows the user to represent relevant morphological elements of the skin (such as the stratum corneum, the hair follicles, and the pilosebaceous glands), and are expected to help with the development of efficient delivery of cosmetic products and medical drugs. The review highlights also several interesting directions for future research in the area of skin xenobiotic penetration made possible by the Computational-Fluid-Dynamics-like modelling category.