title: Synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and its inhibition of liver cancer characteristics in vitro and in vivo.
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.
authors.affiliation: Department of General Surgery, Pudong New Area District Zhoupu Hospital, Shanghai 201318, China.
authors.forename: Mingrong
authors.initials: M
authors.lastname: Cheng
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Gao
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Houxiang
authors.initials: H
authors.lastname: Chen
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Xu
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Li
authors.forename: Jiang
authors.initials: J
authors.lastname: Han
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D002460:Cell Line; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005472:Fluorouracil / Q000737:chemistry* / Q000494:pharmacology*; D006034:Glycyrrhetinic Acid / Q000737:chemistry*; D006801:Humans; D008099:Liver / Q000187:drug effects; D008113:Liver Neoplasms / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size
chemical_list: D004337:Drug Carriers; D048271:Chitosan; D006034:Glycyrrhetinic Acid; D005472:Fluorouracil
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