Box–behnken Design-Guided Development of a Pegylated Liposomal Gel of Α-Terpineol for Enhanced Topical Bioavailability

Background: α-Terpineol, a bioactive compound with antioxidant and anti-inflammatory properties, exhibits limited bioavailability. Liposomal formulations can improve its therapeutic efficacy by enhancing encapsulation, stability, and tissue penetration. To develop and optimize α-terpineol-loaded liposomes using a Box–Behnken design (BBD) for improved bioavailability and therapeutic performance. Materials and methods: Liposomes were prepared by the ethanol injection technique and optimized using a 3-factor, 3-level BBD, with the concentration of phospholipids, cholesterol concentration and sonication as independent variables. Vesicle size, efficiency of capture, releasing drug in vitro, antioxidant test (DPPH assay), dermatokinetic & the stability of formulations were assessed. Results: A vesicle size of 197.4 nm and high entrapment efficiency were obtained with the optimized formulation. In vitro relaxation has shown a permanent profile, with 70.95% of alpha-terpineol released for 24 hrs. Antioxidant activity was significantly higher (92.32%) compared to ascorbic acid (86.98%). Dermatokinetic studies confirmed enhanced tissue penetration, while stability studies indicated preservation of physicochemical properties over time. Conclusion: The optimized α-terpineol-loaded liposomal formulation demonstrated sustained release, superior antioxidant activity, improved tissue penetration, and good stability. These findings emphasize its potential to increase the biological availability and therapeutic efficacy of alpha-terpineol in clinical applications.