Insights into skin permeation enhancement using neoteric solvents: An ATR-FTIR study on human stratum corneum

Discovering new Chemical Permeation Enhancers (CPEs) as excipients has the potential to broaden the spectrum of pharmaceutical drugs, which is currently restricted to small lipophilic molecules. In this context, Deep Eutectic Solvents (DESs), cyclodextrin-based SUPRAmolecular Deep Eutectic Solvents (SUPRADESs), and Choline-based Ionic Liquids (Ch-ILs) were investigated as potential permeation enhancer excipients. Attenuated Total Reflectance - Fourier Transform Infrared (ATR-FTIR) spectroscopy was used to evaluate their effects on human stratum corneum, focusing on quantifying the lipid matrix content and the keratin α-helix/β-sheet ratio. Our findings showed that hydrophilic DESs and SUPRADESs containing polyols, like propylene glycol (1,2-propanediol), glycerol or polyethylene glycol 400, were most effective, simultaneously stabilizing keratin and fluidizing the intercellular lipid matrix. Among the SUPRADESs, HP-βCD/PG stands out by exhibiting an extracting character rather than a fluidizing one, while still stabilizing the keratin fibres. In contrast, mixtures with hydrophobic ammonium or phosphonium salts, like tetraoctylammonium chloride or trihexyltetradecylphosphonium chloride, were identified as potentially more irritating to the skin. • Exploration of DESs, SUPRADESs, and ILs as novel excipients to enhance skin permeation. • ATR-FTIR was used to assess the impact on the lipid matrix and keratin structure. • DESs and SUPRADESs based on hydrophilic polyols showed greater potential. • SUPRADES HP-βCD/PG exhibited unique extraction behavior while stabilizing keratin. • Hydrophobic cations are associated with a higher risk of skin irritation.