In silico study on the contribution of the follicular route to dermal permeability of small molecules

TL;DR

This in silico study explores how the hair follicle influences dermal permeability of small molecules, revealing that its contribution varies with the permeant's physico-chemical properties and emphasizing the need for detailed characterization in permeability assessments.

Contribution

The study introduces a computational approach to quantify the follicular route's role in dermal permeation, highlighting the importance of physico-chemical parameters.

Findings

Follicular contribution varies from negligible to significant.

Permeant properties modulate follicular permeation.

Sample handling affects in vivo and in vitro permeability data.

Abstract

Purpose. This study investigates in silico the contribution of the hair follicle to the overall dermal permeability of small molecules, as published experimental work provides inconclusive information on whether the follicular route favours the permeation of hydrophobic or hydrophilic permeants. Method. A study is conducted varying physico-chemical parameters of permeants such as lipophilicity, molecular weight and protein binding. The simulated data is compared to published experimental data to discuss how those properties can modulate the contribution of the hair follicle to the overall dermal permeation. Results. The results indicate that the contribution of the follicular route to dermal permeation can range from negligible to notable depending on the combination of lipophilic/hydrophilic properties of the substance filling the follicular route and the permeant. Conclusion. Characterisation of the substance filling the follicular route is required for analysing the experimental data of dermal permeation of small molecules, as changes between in vivo and in vitro due to handling of samples and cessation of vital functions can modify the contribution of the follicular route to overall dermal permeation, hence hindering data interpretation.