title: Preliminary pharmacology of galactosylated chitosan/5-fluorouracil nanoparticles and its inhibition of hepatocellular carcinoma in mice.
abstract: Biodegradable polymer nanoparticle drug delivery systems are characterized by targeted drug delivery, improved pharmacokinetic and biodistribution, enhanced drug stability and lowered side effects; these drug delivery systems are widely used for delivery of cytotoxic agents. The galactosylated chitosan (GC)/5-fluorouracil (5-FU) nanoparticle is a nanomaterial made by coupling GC, a polymer known to have the advantages described above, and 5-FU. The GC/5-FU nanoparticle is a sustained release system, it was showed that the peak time, half-life time, mean residence time (MRT) and area of under curve (AUC) of GC/5-FU were longer or more than those of the 5-FU group, but the maximum concentration (Cmax) was lower. The distribution of GC/5-FU in vivo revealed the greatest accumulation in the hepatic cancer tissues, and the hepatic cell was the target of the nanoparticles. Toxicology research showed that the toxicity of GC-5-FU was lower than that of 5-FU in mice. In vivo experiments showed that GC/5-FU can significantly inhibit tumor growth in an orthotropic liver cancer mouse model. GC/5-FU treatment can significantly lower the tumor weight and increase the survival time of mice when compared with 5-FU treatment alone. Flow cytometry and the TUNEL assay revealed that compared with 5-FU, GC/5-FU caused higher rates of G 0-G 1 arrest and apoptosis in hepatic cancer cells.
authors.affiliation: Department of General Surgery, Zhoupu Hospital of Shanghai Pudong New Area, Shanghai, China.
authors.forename: Mingrong
authors.initials: M
authors.lastname: Cheng
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Wan
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.forename: Bingbing
authors.initials: B
authors.lastname: Zha
authors.forename: Jiang
authors.initials: J
authors.lastname: Han
authors.forename: Houxiang
authors.initials: H
authors.lastname: Chen
authors.forename: Fengxiao
authors.initials: F
authors.lastname: Yang
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Xu
authors.forename: Tao
authors.initials: T
authors.lastname: Ye
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems; D005472:Fluorouracil / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D008113:Liver Neoplasms / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000627:therapeutic use*
chemical_list: D000964:Antimetabolites, Antineoplastic; D048271:Chitosan; D005472:Fluorouracil