Development of a Two-Dimensional Model for Predicting Transdermal Permeation with the Follicular Pathway: Demonstration with a Caffeine Study

In 2017, researchers developed a two-dimensional model to predict transdermal permeation through the skin, specifically focusing on the follicular pathway. The model was tested using caffeine and found that the follicular route significantly contributes to systemic bioavailability, predicting a 20% higher maximum concentration of caffeine in the bloodstream when hair follicles are open versus when they are blocked. The study, which involved six healthy volunteers, demonstrated that the model could accurately predict plasma concentrations of caffeine and emphasized the importance of the follicular pathway in the bioavailability of substances after dermal exposure. The model's sensitivity analysis indicated that changes in the diffusion coefficient of caffeine in sebum could significantly affect penetration rates. The study aimed to improve in silico screening for pharmaceuticals and reduce reliance on animal models, although further validation with more compounds was necessary. The research was supported by the UK Biotechnology and Biological Sciences Research Council and Unilever Research Colworth, UK.