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Liposomal Oxymatrine in Hepatic Fibrosis Treatment: Formulation, In Vitro and In Vivo Assessment

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Abstract

The aim was to develop a liposomal oxymatrine conjugating d-alpha tocopheryl polyethylene glycol 1000 succinate (OMT-LIP) for enhanced therapeutics of hepatic fibrosis. OMT-LIP was prepared using the remote loading method. The influences of formulation compositions on the encapsulation efficiency of OMT-LIP were investigated. Mean particle size, zeta potential, morphology, in vitro release, fibrotic liver targeting, and therapeutics of OMT-LIP were thoroughly assessed. The intraliposomal buffer composition and concentration, extraliposomal phase composition and pH, types of phospholipid, lipid molar ratio composition, and theoretical drug loading are crucial factors to entrap OMT into liposomes. The optimum OMT-LIP presented spherically unilamellar microstructures with entrapment efficiency of 79.7 ± 3.9%, mean particle size of 121.6 ± 52.9 nm, and zeta potential of −5.87 mV. OMT-LIP significantly increased the accumulation of OMT in the fibrotic liver with an 11.5-fold greater AUC than OMT solution in the dimethylnitrosamine (DMN)-induced hepatic fibrosis animals. OMT-LIP could be a potential strategy to improve treatment outcomes for hepatic fibrosis, showing the protective effects to mice given CCl4 and the enhanced therapeutics to mice with either DMN or CCl4-induced hepatic fibrosis.

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ACKNOWLEDGMENTS

This work was supported by the Chinese Traditional Medicine Bureau of Zhejiang Province grant (2006C154), Science Technology Department of Zhejiang Province grant (2009F70017), and the analytical funding from Zhejiang University of Technology. The authors are grateful to Dr. Ximei Wu of the Zhejiang University School of Medicine for his technical help in liver histological sections.

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Authors and Affiliations

  1. College of Pharmaceutical Sciences, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou, 310032, People’s Republic of China

    Shujuan Zhang, Tiechuang Wang, Lina Jin, Dandan Shu, Weiguang Shan & Subin Xiong

  2. College of Pharmacy, University of South Carolina, Greenville, South Carolina, 29605, USA

    Jun Wu

  3. Center of Analysis and Measurement, Zhejiang University, 268 Kaixuan Road, Hangzhou, 310029, People’s Republic of China

    Hua Wang

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  1. Shujuan Zhang
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  2. Jun Wu
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  3. Hua Wang
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  4. Tiechuang Wang
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  7. Weiguang Shan
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  8. Subin Xiong
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Correspondence to Subin Xiong.

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Zhang, S., Wu, J., Wang, H. et al. Liposomal Oxymatrine in Hepatic Fibrosis Treatment: Formulation, In Vitro and In Vivo Assessment. AAPS PharmSciTech 15, 620–629 (2014). https://doi.org/10.1208/s12249-014-0086-y

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  • DOI: https://doi.org/10.1208/s12249-014-0086-y

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