Preparation of the Levo-Tetrahydropalmatine Liposome Gel and Its Transdermal Study
Guizhen Zhang, Xuejian Li, Chunyun Huang, Yuanyuan Jiang, Jian Su, Ying Hu
Abstract
Purpose: The aim of this study was to develop a liposome gel containing levo -tetrahydropalmatine ( l -THP) and evaluate its transdermal properties. Methods: A L 16 (4 3 ) orthogonal experiment was conducted to optimize the preparation of l -THP liposomes and assess their characterization and stability in a gel. The transdermal features were analyzed through in vivo and in vitro experiments on rats and Strat-M ® membrane, respectively. The metabolism of l -THP in liver and skin S9 fractions was also studied. Results: The optimization of the orthogonal experiment revealed that the ideal mass ratio of phosphatidylcholine, cholesterol, and l -THP during preparation was 10:1:3. The resulting liposome exhibited a particle size of 68 nm, a PDI of 0.27, a drug loading of 4.33%, an encapsulation of 18.79%, and a zeta potential of − 41.27 mV. Both the l -THP and its liposome-gel formulation were found to be stable for a duration of 45 days at 4 °C and 30 °C. During the in vivo transdermal study, the maximum concentration (C max ) of l -THP from the liposome gel was 0.16 μg/mL, and the time to reach this maximum concentration (t max ) was 1.2 hours. The relative bioavailability of l -THP in the liposome gel was 233.8% compared to the emulsion. The concentration of l -THP (prepared in PBS) decreased at a rate of 0.0067 μg/mL/min in the liver S9 fraction and 0.0027 μg/mL/min in the skin S9 fraction, however, this difference was not observed when l -THP was encapsulated in liposomes. l -THP passed through the Strat-M ® membrane at a rate of 0.0032 mg/cm 2 /h and 0.002 mg/cm 2 /h for the emulsion and liposome gel, respectively. Conclusion: The optimal process for the preparation of l -THP liposomes was obtained. Compared to the emulsion, the liposomes provided greater bioavailability when used transdermally. The liposomes also provided greater stability for l -THP during storage. Graphical Abstract: Keywords: liposome, transdermal property, l -tetrahydropalmatine, S9 fraction, orthogonal experiment, stability