Evaluation of terpene-based hydrophobic deep eutectic solvents as skin permeation enhancers

Abstract We investigated whether carboxylic acid-terpene-based deep eutectic solvents (DESs) can be used as skin permeation enhancers. We performed transdermal experiments, and their results showed that DESs with longer hydrocarbon chains can enhance the skin permeability of hydrophilic fluorescein sodium and hydrophobic meloxicam. Additionally, all DESs could improve the skin permeability of poorly soluble resveratrol. Subsequently, we evaluated the stratum corneum’s structural transition after applying DESs. The results showed that the l-menthol-based DESs with longer hydrocarbon chains disrupt lipid layers more than those with shorter hydrocarbon chains. Thymol-based DES extracted the lipids in the stratum corneum and permeated the corneocytes. Transepidermal water loss measurements showed that l-menthol-based DESs with longer hydrocarbon chains and thymol-based DESs damage skin as they disturb the inner parts of stratum corneum lipids. Overall, we concluded that DESs with longer hydrocarbon chains can be used as skin permeation enhancers for various drugs by reducing skin irritation.