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Mar. Drugs 2013, 11(9), 3517-3536; doi:10.3390/md11093517
Article

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

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Received: 16 August 2013; in revised form: 1 September 2013 / Accepted: 2 September 2013 / Published: 17 September 2013
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Abstract: 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.
Keywords: hepatic carcinoma; regulatory T-cells; glycyrrhetinic acid; targeted therapy; 5-fluorouracil hepatic carcinoma; regulatory T-cells; glycyrrhetinic acid; targeted therapy; 5-fluorouracil
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Cheng, M.; Gao, X.; Wang, Y.; Chen, H.; He, B.; Xu, H.; Li, Y.; Han, J.; Zhang, Z. Synthesis of Glycyrrhetinic Acid-Modified Chitosan 5-Fluorouracil Nanoparticles and Its Inhibition of Liver Cancer Characteristics in Vitro and in Vivo. Mar. Drugs 2013, 11, 3517-3536.

AMA Style

Cheng M, Gao X, Wang Y, Chen H, He B, Xu H, Li Y, Han J, Zhang Z. Synthesis of Glycyrrhetinic Acid-Modified Chitosan 5-Fluorouracil Nanoparticles and Its Inhibition of Liver Cancer Characteristics in Vitro and in Vivo. Marine Drugs. 2013; 11(9):3517-3536.

Chicago/Turabian Style

Cheng, Mingrong; Gao, Xiaoyan; Wang, Yong; Chen, Houxiang; He, Bing; Xu, Hongzhi; Li, Yingchun; Han, Jiang; Zhang, Zhiping. 2013. "Synthesis of Glycyrrhetinic Acid-Modified Chitosan 5-Fluorouracil Nanoparticles and Its Inhibition of Liver Cancer Characteristics in Vitro and in Vivo." Mar. Drugs 11, no. 9: 3517-3536.



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