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.; YANIS ESPINOSA, R.; FANANI, M.L.; ÁLVAREZ, A.

Rosario

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 delivery efficiency. In the present work, we have approached the study of two arginine-based amphiphiles synthesized in our laboratory as potential CPE and their interaction with a stratum corneum lipid membrane model (SCM) from two complementary perspectives. Nα-benzoyl arginine decyl- and dodecylamide (Bz-Arg-NHC10 and Bz-Arg-NHC12) were tested in comparison with the classical enhancer oleic acid (OA), and the non-enhancer stearic acid (SA). Experiments involved the use of lipid monolayers, taken as models of the unit 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 SCM monolayers, it lacked the capacity to increase the film elasticity. Furthermore, MD results revealed a reduction of the carbon–hydrogen bond order parameters for the components of 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 affected the lateral structure of heterogeneous SC membranes at the nanoscale by relaxing and rounding the domain’s borders. These effects may lead to destabilization of the lamellar structure of the SC at the microscale as well as the alteration of in-plane lateral nanostructure and promotion of thinner, more interconnected, and permeable SC layers, which might be of fundamental importance in the permeation enhancement function.