Theoretical Investigation on the Construction of Hair Follicle Membranes and the Transdermal Drug Delivery Mechanisms of JAK Inhibitors via Distinct Pathways

This study investigates the transdermal drug delivery mechanisms of JAK inhibitors through hair follicle (HF) membranes using molecular dynamics simulations. A model composed of 15 lipid molecules was constructed to explore the uptake processes of three JAK inhibitors: Ruxolitinib, Baricitinib, and Momelotinib. The research revealed distinct uptake mechanisms between the stratum corneum (SC) and HF. While the SC utilizes cholesterol-mediated absorption via sterol caveolae, the HF membrane exhibits an additional Lift Route, where JAK inhibitors interact directly with phospholipid headgroups, providing an extra permeation pathway. These findings offer molecular insights into the differential uptake mechanisms, enhancing the understanding of transdermal drug delivery.