Water soluble multiarm-polyethylene glycol–betulinic acid prodrugs: design, synthesis, and in vivo effectiveness

Lin Dai; Dan Li; Jing Cheng; Jing Liu; Li-Hong Deng; Lu-Ying Wang; Jian-Du Lei; Jing He

doi:10.1039/C4PY00648H

Water soluble multiarm-polyethylene glycol–betulinic acid prodrugs: design, synthesis, and in vivo effectiveness

Lin Dai,^a Dan Li,^a Jing Cheng,^a Jing Liu,^a Li-Hong Deng,^a Lu-Ying Wang,^a Jian-Du Lei*^a and Jing He*^a

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* Corresponding authors

^a Beijing Key Laboratory of Lignocellulosic Chemistry, Beijing Forestry University, Beijing 100083, P. R. China
E-mail: ljd2012@bjfu.edu.cn, hejing2008@sina.com
Fax: +86-10-62338152
Tel: +86-10-62338152

Abstract

Betulinic acid (BA) is a new type of cancer-fighting drug, but it is limited by its low water solubility and relatively short half-life in clinical applications. To overcome the shortcomings, BA prodrugs were prepared by using multiarm-polyethylene glycol linkers. The prodrugs exhibited high drug loading capacity (3.26–11.81 wt%), high water solubility (290–750 fold of free BA), and excellent in vitro anticancer activity. Subsequent tumor xenograft assays demonstrated the superior therapeutic effect of BA prodrugs on inhibition of tumor growth compared with free BA. Multiple intravenous injection of BA prodrugs equivalent to 10 mg of BA per kg resulted in the decrease of an established implanted murine Lewis lung carcinoma (percent tumor growth inhibition after treatment on day 20, 72.1–90.7%) in mice. These results strongly supported that the BA prodrugs are promising for cancer therapy.

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The article was received on 09 May 2014, accepted on 12 Jun 2014 and first published on 13 Jun 2014

Article type: Paper

DOI: 10.1039/C4PY00648H

Author version available: Download Author version (PDF)

Citation: Polym. Chem., 2014,5, 5775-5783

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Water soluble multiarm-polyethylene glycol–betulinic acid prodrugs: design, synthesis, and in vivo effectiveness

L. Dai, D. Li, J. Cheng, J. Liu, L. Deng, L. Wang, J. Lei and J. He, Polym. Chem., 2014, 5, 5775
DOI: 10.1039/C4PY00648H
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Polymer Chemistry

Water soluble multiarm-polyethylene glycol–betulinic acid prodrugs: design, synthesis, and in vivo effectiveness

Abstract

Supplementary files

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Water soluble multiarm-polyethylene glycol–betulinic acid prodrugs: design, synthesis, and in vivo effectiveness

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