The Ultrastructural Changes of Stratum Corneum Lipids after Application of Oleic Acid in Propylene Glycol

ABSTRACT

BACKGROUND: 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. OBJECTIVE: The purpose of this study was to assess the interaction between oleic acid and stratum corneum lipids in vivo. METHODS: 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. RESULTS: 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. CONCLUSION: 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.