Development of Oleic Acid Composite Vesicles as a Topical Delivery System: An Evaluation of Stability, Skin Permeability, and Antioxidant and Antibacterial Activities

Fatty acid vesicles (FAVs) are promising nanocarriers, but their application is limited by a narrow, alkaline pH formation window that mismatches the weak acidity of physiological environments, such as skin. To overcome this, we developed composite vesicles using oleic acid (OA) and the non-ionic surfactant Tween 40 (TW40). pH titration confirmed that the OA/TW40 system successfully broadened the vesicle formation window from 8.2–10.08 to 3.1–7.2, aligning it with the physiological pH range. The bioactive flavonoid luteolin (LUT) was efficiently encapsulated into these OA/TW40-FAVs, achieving a high encapsulation efficiency (EE) of 87.13% and a drug loading capacity (DLC) of 9.58. The formulation demonstrated superior topical delivery performance: the cumulative transdermal flux (933.08 µg·cm−2) and skin retention (68.18 µg·cm−2) were both approximately double that of the free LUT solution. Furthermore, the OA/TW40/LUT-FAVs provided sustained drug release and exhibited synergistically enhanced antioxidant and antimicrobial activities compared to free LUT or blank vesicles. Collectively, these findings establish OA/TW40 composite vesicles as a robust and efficient nanoplatform for the topical delivery of bioactive compounds.