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Chitosan-Coated Liposomes: The Strategy to Reduce Intestinal Toxicity and Improve Bioavailability of Oral Vinorelbine

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Abstract

In recent years, the oral administration of vinorelbine has gradually replaced intravenous administration in the treatment of several types of tumors. Even though the risk of phlebitis is avoided with oral administration, oral vinorelbine is still not a highly patient-compliant route due to the severe gastrointestinal toxicity. Vinorelbine-loaded liposomes with high encapsulation efficiency and suitable particle size were prepared using the ammonium sulfate gradient method. Chitosan-coated liposomes showed the slowest in vitro release compared to uncoated liposomes and vinorelbine solution. No damage was observed in the intestinal epithelial cells of mice orally administered with coated vinorelbine liposomes due to the low presence of the free drug in the gastrointestinal tract and the LD50 was increased from 129.83 to 182.25 mg/kg compared to oral vinorelbine solution. In addition, the positive surface potential of chitosan-coating endowed liposomes with mucosal adhesive function, delaying the time to reach the peak plasma concentration of vinorelbine from 1 to 4 h after administration. And bioavailability was increased to 2.1-fold compared to vinorelbine solution. In short, a new strategy to address the severe gastrointestinal side effects of oral vinorelbine has been developed.

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Funding

This work was supported by PhD Research Startup Foundation of Liaoning Province (2020BS-128), National Key R&D Program of China (No. 2020YFE0201700), National Mega-project for Innovative Drugs (No.2019ZX09721001), Liaoning Revitalization Talents Program (XLYC1908031), and National Natural Science Foundation of China (81673378).

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Author notes

  1. Chen Guo and **chun Zhu contributed equally.

Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, Liaoning, People’s Republic of China

    Chen Guo, Haoyang Yuan, Haoyu Liu, Yu Zhang, Haibing He, **gxin Gou & **ng Tang

  2. Center for Drug and Cosmetic Safety Evaluation and Research, Gansu Provincial Institute of Drug Control, 7 Yinan Road, Anning District, Lanzhou, 730070, Gansu, People’s Republic of China

    **chun Zhu

  3. School of Functional Food and Wine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, Liaoning, People’s Republic of China

    Tian Yin

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  1. Chen Guo
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Contributions

Chen Guo: acquisition, analysis, interpretation, and drafting the work; **chun Zhu: acquisition, analysis, and interpretation; Haoyang Yuan: acquisition, analysis; Haoyu Liu: acquisition, analysis; Tian Yin: analysis, interpretation; Yu Zhang: analysis, interpretation; Haibing He: analysis, interpretation; **gxin Gou: design of the work, analysis, interpretation, and drafting the work. **ng Tang: design of the work, analysis, interpretation, and drafting the work.

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Correspondence to **gxin Gou or **ng Tang.

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Guo, C., Zhu, X., Yuan, H. et al. Chitosan-Coated Liposomes: The Strategy to Reduce Intestinal Toxicity and Improve Bioavailability of Oral Vinorelbine. AAPS PharmSciTech 23, 163 (2022). https://doi.org/10.1208/s12249-022-02308-7

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