Preparation of the Levo-Tetrahydropalmatine Liposome Gel and Its Transdermal Study

Abstract

Guizhen Zhang,1,* Xuejian Li,1,* Chunyun Huang,1 Yuanyuan Jiang,1 Jian Su,1 Ying Hu2 1Guangxi Scientific Research Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China; 2Faculty of Pharmacy, Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian Su, Guangxi Key Laboratory of Zhuang and Yao Ethnic Medicine, Guangxi Scientific Research Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, 13 Wuhe Avenue, Nanning, Guangxi, 530200, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected] Ying Hu, Department of Pharmacology, Faculty of Pharmacy, Guangxi University of Chinese Medicine, 13 Wuhe Avenue, Nanning, Guangxi, 530200, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected]: The aim of this study was to develop a liposome gel containing levo-tetrahydropalmatine (l-THP) and evaluate its transdermal properties.Methods: A L16 (43) 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 (Cmax) of l-THP from the liposome gel was 0.16 μg/mL, and the time to reach this maximum concentration (tmax) 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/cm2/h and 0.002 mg/cm2/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

Keywords

• liposome
• transdermal property
• l-tetrahydropalmatine
• s9 fraction
• orthogonal experiment
• stability