Mathematical modelling of transdermal permeation of chemicals with special focus on the hair follicle pathway.

The assessment of the follicular penetration of chemicals into the human skin is of high importance to topical and transdermal drug delivery, personal care, as well as risk assessment of chemical exposure. This is due to the significant contribution of the hair follicles to the penetration of chemicals through the epidermal barrier. The purpose of this work is to develop a two-dimensional pharmacokinetic model which will provide quantitative elucidation of the impact of the follicular pathway, in addition to the transcellular and intercellular routes, on a wide range of chemicals. The follicular pathway is modelled by diffusion in the sebum, which is assumed to completely fill the gap between the inner and outer root sheath. The model is capable of predicting the transdermal permeation kinetics by using built-in equations to estimate the input parameters (e.g. the partition and diffusion coefficients in various skin components). The model has been quantitatively or qualitatively compared to 18 experimental studies, and has demonstrated good predictive capability against the majority of the experimental data. Simulations across a wide chemical space have indicated that the follicular pathway has a greater impact on the penetration of lipophilic than hydrophilic chemicals. Additionally, the larger the molecular weight of the chemical, the greater the impact the hair follicle has on its penetration. The follicular impact has been quantified in various ways (e.g. amount penetrated, bioavailability, permeability difference). The developed model can provide new insight and detailed information regarding chemicals’ disposition and localised delivery in lipid, corneocytes, viable dermis, dermis and the hair follicle

Development of a two-dimensional model for predicting transdermal permeation with the follicular pathway: Demonstration with a caffeine study

Purpose: The development of a new two-dimensional (2D) model to predict follicular permeation, with integration into a recently reported multi-scale model of transdermal permeation is presented. Methods: The follicular pathway is modelled by diffusion in sebum. The mass transfer and partition properties of solutes in lipid, corneocytes, viable dermis, dermis and systemic circulation are calculated as reported previously [Pharm Res 33 (2016) 1602]. The mass transfer and partition properties in sebum are collected from existing literature. None of the model input parameters was fit to the clinical data with which the model prediction is compared. Results: The integrated model has been applied to predict the published clinical data of transdermal permeation of caffeine. The relative importance of the follicular pathway is analysed. Good agreement of the model prediction with the clinical data has been obtained. The simulation confirms that for caffeine the follicular route is important; the maximum bioavailable concentration of caffeine in systemic circulation with open hair follicles is predicted to be 20% higher than that when hair follicles are blocked. Conclusions: The follicular pathway contributes to not only short time fast penetration, but also the overall systemic bioavailability. With such in silico model, useful information can be obtained for caffeine disposition and localised delivery in lipid, corneocytes, viable dermis, dermis and the hair follicle. Such detailed information is difficult to obtain experimentally

Development of a two-dimensional model for predicting transdermal permeation with the follicular pathway: Demonstration with a caffeine study

Purpose: The development of a new two-dimensional (2D) model to predict follicular permeation, with integration into a recently reported multi-scale model of transdermal permeation is presented. Methods: The follicular pathway is modelled by diffusion in sebum. The mass transfer and partition properties of solutes in lipid, corneocytes, viable dermis, dermis and systemic circulation are calculated as reported previously [Pharm Res 33 (2016) 1602]. The mass transfer and partition properties in sebum are collected from existing literature. None of the model input parameters was fit to the clinical data with which the model prediction is compared. Results: The integrated model has been applied to predict the published clinical data of transdermal permeation of caffeine. The relative importance of the follicular pathway is analysed. Good agreement of the model prediction with the clinical data has been obtained. The simulation confirms that for caffeine the follicular route is important; the maximum bioavailable concentration of caffeine in systemic circulation with open hair follicles is predicted to be 20% higher than that when hair follicles are blocked. Conclusions: The follicular pathway contributes to not only short time fast penetration, but also the overall systemic bioavailability. With such in silico model, useful information can be obtained for caffeine disposition and localised delivery in lipid, corneocytes, viable dermis, dermis and the hair follicle. Such detailed information is difficult to obtain experimentally