Synthesis of Glycyrrhetinic Acid-Modified Chitosan 5-Fluorouracil Nanoparticles and Its Inhibition of Liver Cancer Characteristics in Vitro and in Vivo

Marine Drugs

Mingrong Cheng²  Xiaoyan Gao³  Yong Wang⁵  Houxiang Chen¹  Bing He⁶  Hongzhi Xu⁶  Yingchun Li⁴  Jiang Han² 

[1] Zhejiang Huafon Fiber Research Institute, Zhejiang Huafon Spandex Co., Ltd, Wenzhou 325200, China; E-Mail:;Department of General Surgery, Pudong New Area District Zhoupu Hospital, Shanghai 201318, China; E-Mails:;Department of Plastic Surgery, Pudong New Area District Zhoupu Hospital, Shanghai 201318, China; E-Mail:;Department of Endoscopy, Pudong New Area District Zhoupu Hospital, Shanghai 201318, China; E-Mail:;School of Materials Science and Engineering, Wuhan University of Technology, Wuhan 430070, China;Department of General Surgery, Shanghai Fifth People’s Hospital, Fudan University, Shanghai 200240, China; E-Mail:

关键词: hepatic carcinoma;    regulatory T-cells;    glycyrrhetinic acid;    targeted therapy;    5-fluorouracil;   

DOI  :  10.3390/md11093517

来源: mdpi

【 摘 要 】

Nanoparticle drug delivery (NDDS) is a novel system in which the drugs are delivered to the site of action by small particles in the nanometer range. Natural or synthetic polymers are used as vectors in NDDS, as they provide targeted, sustained release and biodegradability. Here, we used the chitosan and hepatoma cell-specific binding molecule, glycyrrhetinic acid (GA), to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS). The synthetic product was confirmed by Fourier transformed infrared spectroscopy (FT-IR) and ¹H-nuclear magnetic resonance (¹H-NMR). By combining GA-CTS and 5-FU (5-fluorouracil), we obtained a GA-CTS/5-FU nanoparticle, with a particle size of 217.2 nm, a drug loading of 1.56% and a polydispersity index of 0.003. The GA-CTS/5-FU nanoparticle provided a sustained release system comprising three distinct phases of quick, steady and slow release. We demonstrated that the nanoparticle accumulated in the liver. In vitro data indicated that it had a dose- and time-dependent anti-cancer effect. The effective drug exposure time against hepatic cancer cells was increased in comparison with that observed with 5-FU. Additionally, GA-CTS/5-FU significantly inhibited the growth of drug-resistant hepatoma, which may compensate for the drug-resistance of 5-FU. In vivo studies on an orthotropic liver cancer mouse model demonstrated that GA-CTS/5-FU significantly inhibited tumor growth, resulting in increased survival time.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.