Interaction of amphiphilic derivatives of Vitamin C with model lipid membranes: a vision of the mechanism for enhanced skin permeation

ZULUETA DÍAZ, YENISLEIDY DE LAS MERCEDES; FANANI, M. LAURA

Berlín

Congreso; Biomembrane days; 2019

Instituto Max Planck de Coloides e Interfaces

The alkyl esters of the L-ascorbic acid (ASCn) are amphiphilic derivatives of Vitamin C, which retain their antioxidant power and have been proposed as enhancers of dermal permeation. In this work we address the question of what are the physical parameters that regulate the incorporation of amphiphilic drugs into lipid membranes, taking the ASCn family as a model. We used lipid monolayer of different composition as biomembrane models and characterized their rheological behavior. We were also interested in the quaternary mixture of the most abundant lipids in stratum corneum (SC). We found a direct correlation between the elasticity of the lipid films and their ability to incorporate ASCn. This result shed light on the understanding of the susceptibility of different membranes to the penetration of amphiphiles. In turn, the incorporation of those drugs into the monolayers turned them more easily compressible. We also investigated if this effect would be related to their capacity to act as enhancers of skin permeation. We found that ASCn, as well as other amphiphilic dermal permeation enhancers, are able to increase the elasticity of membranes that simulate SC, making it more susceptible to the incorporation of other drugs of interest in the dermal permeation process. Finally, we found that ASCn, as well as the classic permeation enhancer oleic acid, induced a two-dimensional restructuring of SC membranes at the nanoscale, enlarging the thinner phase of the heterogeneous SC membranes. Our studies based on the observations of the principles of amphiphilic drug-lipid membrane interaction, allow a deeper understanding of the action of the amphiphilic dermal permeation enhancers on the properties of SC. This opens the possibility of a rational search for new compounds with specific characteristics and pharmacological function.