New trends in mechanistic transdermal drug delivery modelling: Towards an accurate geometric description of the skin microstructure

Abstract

Interest for in silico modelling of the penetration of xenobiotics into the skin has been growing in the last years, owing to their lower cost compared to in vitro alternatives, and the need for avoiding animal experimentation. This review presents an overview of Physiologically-Based Pharmacokinetic (PBPK) models and focuses on models based on the Finite Element, Finite Volume and Lattice Boltzmann methods. These three methods are commonly encountered in flow and solid mechanics and are becoming more popular in bioengineering, too, because they allow a detailed geometric representation of the skin microstructure, contrarily to QSAR and compartmental models. The geometry of microstructural features such as the stratum corneum (i.e. by means of the ‘bricks and mortar’ model) and the skin appendages (e.g. hair follicles, and the pilosebaceous unit) allowing realistic visualization of pharmaco-kinetic phenomena. This review also highlights several perspectives to further develop these models in directions relevant to industry.