Multiscale Modeling of Molecule Transport through Skin’s Deeper Layers

Abstract

Accurate in-silico models of human skin are required to obtain the uptake/release of molecules across the skin layers to supplement the in-vivo/in-vitro experiments for faster development/testing of cosmetics and drugs. We aim to develop an in-silico skin permeation model by extending the multiscale modeling framework developed earlier for skin’s top layer to deeper layer and compared the outcomes with in-vitro experimental permeation data of 43 cosmetic-relevant molecules across human skin. In this study, we have extended a multiscale modeling framework, with realistic heterogeneous stratum corneum (SC) comprising of network of permeable lipids and corneocytes, followed by homogeneous viable epidermis and dermis. The diffusion coefficients of molecules in lipid layer were determined using molecular dynamics simulations, whereas the diffusion coefficients in other layers and all the partition coefficients were calculated from correlations reported in literature. These parameters were then used in the macroscopic models to predict the release profiles of drugs through the deeper skin layers. The obtained release profiles were in good agreement with available experimental data for most of the molecules. The reported model could provide insight into cosmetics/drugs skin permeation and act as a time-saving and efficient guiding tool for performing targeted experiments