Arginine-based surfactants alter the rheological and inplane structural properties of stratum corneum model membranes

HERMET, M.; FAIT, M.E.; ZULUETA DÍAZ, Y.M.; MORCELLE, S.R.; ESPINOSA, Y.R.; FANANI, M.L.; ALVAREZ, A.

Congreso; L REUNIÓN ANUAL SAB; 2022

Sociedad Argentina de Biofísica

Surfactants represent one of the most employed chemical permeation enhancers (CPE)used to overcome the barrier function of the skin in order to improve transdermal deliveryefficiency. In the present work, we have approached the study of two arginine-basedamphiphiles synthesized in our laboratory as potential CPE and their interaction with astratum corneum lipid membrane model (SCM) from two complementary perspectives.Nα-benzoyl arginine decyl- and dodecylamide (Bz-Arg-NHC10 and Bz-Arg-NHC12) weretested in comparison with the classical enhancer oleic acid (OA), and the non-enhancerstearic acid (SA). Experiments involved the use of lipid monolayers, taken as models of theunit film layer of the stratum corneum (SC), and atomistic Molecular Dynamics (MD)simulations. Both approaches evidenced that the amphiphiles studied alter therheological and structural properties of SCM membrane, increasing its elasticity.Conversely, although SA showed a higher tendency to be incorporated into the SCMmonolayers, it lacked the capacity to increase the film elasticity. Furthermore, MD resultsrevealed a reduction of the carbon–hydrogen bond order parameters for the componentsof the SCM membrane triggered by the incorporation of Bz-Arg-NHC10 or Bz-Arg-NHC12 even more pronounced than when the enhancer OA was present.In summary, the arginine-based surfactants induced disorder of the lipid chains,enhancing membrane elasticity, and thinning the overall membrane. They also affectedthe lateral structure of heterogeneous SC membranes at the nanoscale by relaxing androunding the domain’s borders. These effects may lead to destabilization of the lamellarstructure of the SC at the microscale as well as the alteration of in-plane lateralnanostructure and promotion of thinner, more interconnected, and permeable SC layers,which might be of fundamental importance in the permeation enhancement function.