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.
Keywords:
5-Fu; GC-FUA nanoparticles; asialoglycoprotein receptor; chitosan; drug delivery system.
MeSH terms
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A549 Cells
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Absorption, Physiological
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Animals
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Antimetabolites, Antineoplastic / administration & dosage*
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Antimetabolites, Antineoplastic / adverse effects
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Antimetabolites, Antineoplastic / pharmacokinetics
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Antimetabolites, Antineoplastic / pharmacology
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Carcinoma, Hepatocellular / drug therapy*
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Carcinoma, Hepatocellular / metabolism
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Cell Survival / drug effects
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Chitosan / administration & dosage*
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Chitosan / adverse effects
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Chitosan / analogs & derivatives*
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Chitosan / pharmacokinetics
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Chitosan / pharmacology
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Drug Carriers / administration & dosage*
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Drug Carriers / adverse effects
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Drug Carriers / pharmacokinetics
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Drug Carriers / pharmacology
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Fluorouracil / administration & dosage*
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Fluorouracil / adverse effects
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Fluorouracil / analogs & derivatives*
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Fluorouracil / pharmacokinetics
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Fluorouracil / pharmacology
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Glycosylation
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Half-Life
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Hemolysis / drug effects
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Hep G2 Cells
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Hepatocytes / drug effects
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Hepatocytes / metabolism
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Humans
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Liver Neoplasms / drug therapy
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Liver Neoplasms / metabolism
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Mice
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Nanoparticles / adverse effects
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Nanoparticles / chemistry*
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Nanoparticles / ultrastructure
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Prodrugs / administration & dosage*
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Prodrugs / adverse effects
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Prodrugs / pharmacokinetics
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Prodrugs / pharmacology
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Rabbits
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Random Allocation
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Rats, Sprague-Dawley
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Tissue Distribution
Substances
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Antimetabolites, Antineoplastic
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Drug Carriers
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Prodrugs
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Chitosan
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Fluorouracil