Impact of propylene glycol, menthol:thymol deep eutectic solvent, and their blends on the structure and molecular mobility of stratum corneum components

This study explored how propylene glycol (PG), menthol:thymol deep eutectic solvent (DES, molar ratio 6:4), and PG:DES blends modulate drug permeation by impacting the stratum corneum (SC). Porcine SC samples were exposed to PG, DES, and PG:DES blends with varying PG content (10%, 50 %, or 90 %). The impact of these formulations on SC lipid extraction, lipid arrangement, and keratin's secondary structure were analyzed using attenuated total reflectance Fourier-transform infrared spectroscopy. PG:DES blends with 10% or 50% PG extracted more SC lipids than pure DES, while pure PG extracted fewer lipids. The formulations also slightly loosened the lipid packing. PG and PG:DES blends promoted the transition of keratin's secondary structure from alpha-helix to beta-sheet. Changes in SC lipid and protein molecular mobility in the presence of the formulations were examined with 13C magic-angle spinning nuclear magnetic resonance spectroscopy. DES significantly increased lipid and protein mobility, while PG had minimal effects. The impact of PG:DES blends on SC mobility depended on DES content, with more DES causing stronger mobility increase. The amount of clotrimazole permeated through the skin correlated with higher beta-sheet keratin fractions, suggesting PG in corneocytes facilitates drug permeation via the intracellular route. Small amounts of DES in blends further enhanced drug and PG passage through intercellular lipids, likely by altering their packing and mobility. In conclusion, the enhanced clotrimazole permeation in PG:DES blends compared to pure PG or DES likely results from PG's action on corneocytes and DES's effect on the lipid matrix.