(757d) Packing, Order, and Interfacial Influences on Permeability through Gel-Phase Lipid Bilayers

Gel-phase lipid bilayers are often used in cosmetic and pharmaceutical formulations as topical treatments aimed at retaining moisture by mimicking the densely packed lipid lamella in the outermost layer of the skin, the stratum corneum. Designing such formulations requires an understanding of the interplay between lipid composition, structure, and permeability. Molecular simulation provides a direct framework to systematically study the influence of such variables on lamella structure and permeability. Molecular dynamics simulations of gel-phase bilayers consisting of 1,2-distearoyl-sn-glycero-3-phosphatidylcholine (DSPC), free fatty acids, and alcohol molecules of varying chain length and concentration have been performed, for both binary and ternary mixtures, to understand the relationships between lipid composition, structure, and permeability in dense gel-phase bilayers. Complex structure-property relationships are identified through statistical analysis and bootstrapping methods to improve the reliability of permeability simulations at reduced computational expense. The influence of DSPC, free fatty acids, and alcohol molecules on bilayer packing, bilayer order, and interfacial water behavior are found to be related to trends in water permeability.