The Interaction of Permeation Enhancers and the Skin Barrier

The stratum corneum (SC), the outermost layer of the skin, acts as an effective barrier to permeation of chemicals both into and out of the skin. Topical drug formulations often include permeation enhancers such as propylene glycol (PG) and isopropanol (IPA) to improve delivery of the active ingredient through the skin barrier. To understand how PEs interact with and influence the structure and organisation of the lipid lamella observed in the SC, molecular dynamics simulations have been conducted to examine the effects of PG and IPA.
Model SC bilayers containing Ceramide Non-hydroxy fatty acid/Sphingosine (Cer[NS]24), lignoceric acid (C24), and cholesterol in a 1:1:0.5 molar ratio have been studied in contact with water containing different concentrations of PG (0–100 weight %) and IPA (0–20 %). PG/water mixtures caused measurable structural changes, including increased area per lipid and reduced bilayer thickness, indicating disruption of lipid packing but limited broadening of the interfacial region. In contrast, IPA was found to have a limited effect on lipid packing but significantly disrupted interfacial order, broadening the interface and increasing lipid mobility.
Solvents containing mixtures of PG and IPA exhibited non-additive effects: the significant interfacial disruption seen with IPA alone was diminished in the presence of PG, while the systems became more structurally heterogeneous. These findings demonstrate that permeation enhancers operate through distinct yet interconnected mechanisms, emphasising how their combined presence modifies bilayer organisation beyond the effects of each component individually. This work adds to a mechanistic framework for understanding enhancer-lipid interactions in the skin barrier.