title: In vitro and in vivo evaluation of macromolecular prodrug GC-FUA based nanoparticle for hepatocellular carcinoma chemotherapy.
abstract: A novel type of macromolecular prodrug delivery system is reported in this research. The N-galactosylated-chitosan-5-fluorouracil acetic acid conjugate (GC-FUA) based nanoparticle delivery system was evaluated in vitro and in vivo. Biocompatibility of GC-FUA-NPs was screened by BSA adsorption test and hemolysis activity examination in vitro. Cytotoxicity and cellular uptake study in HepG2 and A549 cells demonstrated that compared to free 5-Fu, the GC-FUA-NPs play great function in killing cancer cells for the cell endocytosis mediated by asialoglycoprotein receptor (ASGPR), which overexpresses on the cell surface. Pharmacokinetics study further illustrated that the drug-loaded nanoparticles has a much longer half-time than free 5-Fu in blood circulation in Sprague-Dawley (SD) rats. Tissue distribution was investigated in Kunming mice, and the result showed that the GC-FUA-NPs have a long circulation effect. The obtained data suggested that GC-FUA-NP is a very promising drug delivery system for efficient treatment of hepatocellular carcinoma.
authors.affiliation: a Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China , Hengyang , China.
authors.forename: Can
authors.initials: C
authors.lastname: Huang
authors.affiliation: b Learning Key Laboratory for Pharmacoproteomics of Hunan Province, Institute of Pharmacy & Pharmacology University of South China , Hengyang , China , and.
authors.forename: Na-Mei
authors.initials: NM
authors.lastname: Li
authors.affiliation: c Chemistry Department, Eastern Kentucky University , Richmond , KY , USA.
authors.forename: Pei
authors.initials: P
authors.lastname: Gao
authors.affiliation: a Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China , Hengyang , China.
authors.forename: Sa
authors.initials: S
authors.lastname: Yang
authors.affiliation: a Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China , Hengyang , China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ning
authors.affiliation: a Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China , Hengyang , China.
authors.forename: Wen
authors.initials: W
authors.lastname: Huang
authors.affiliation: a Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China , Hengyang , China.
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Li
authors.affiliation: a Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China , Hengyang , China.
authors.forename: Peng-Ju
authors.initials: PJ
authors.lastname: Ye
authors.affiliation: a Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China , Hengyang , China.
authors.forename: Li
authors.initials: L
authors.lastname: Xiang
authors.affiliation: a Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China , Hengyang , China.
authors.forename: Dong-Xiu
authors.initials: DX
authors.lastname: He
authors.affiliation: a Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China , Hengyang , China.
authors.forename: Xiang-Wen
authors.initials: XW
authors.lastname: Tan
authors.affiliation: a Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China , Hengyang , China.|b Learning Key Laboratory for Pharmacoproteomics of Hunan Province, Institute of Pharmacy & Pharmacology University of South China , Hengyang , China , and.
authors.forename: Cui-Yun
authors.initials: CY
authors.lastname: Yu
mesh_terms: D000072283:A549 Cells; D065567:Absorption, Physiological; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D006031:Glycosylation; D006207:Half-Life; D006461:Hemolysis / Q000187:drug effects; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry* / Q000648:ultrastructure; D011355:Prodrugs / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D011817:Rabbits; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D011355:Prodrugs; D048271:Chitosan; D005472:Fluorouracil
keywords: 5-Fu; GC-FUA nanoparticles; asialoglycoprotein receptor; chitosan; drug delivery system