The stratum corneum presents a significant barrier to transdermal drug delivery. Approaches to improve percutaneous absorption of drugs have included iontophoresis and skin penetration enhancers. Oleic acid has been studied as a skin penetration enhancer for drugs, primarily via its action mainly on the stratum corneum lipid structure.

The purpose of this study was to assess the interaction between oleic acid and stratum corneum lipids in vivo.

Male hairless mice were treated topically with oleic acid. Barrier function was assessed by transepidermal water loss measurement and ultrastructural observation with ruthenium tetroxide (RuO₄) staining.

Oleic acid in propylene glycol had a profound effect on epidermal barrier function and was found to be concentration dependent. Moreover, ultrastructural examination with RuO4 post-fixation demonstrated that there were marked alterations in the stratum corneum lipid structure.

This study provides direct evidence that oleic acid increases the epidermal permeability through a mechanism involving the stratum corneum lipid membrane perturbation via the lacunae formation within the stratum corneum.