In vitro and in vivo evaluation of macromolecular prodrug GC-FUA based nanoparticle for hepatocellular carcinoma chemotherapy

Drug Delivery

Pei Gao¹  Xiang-Wen Tan²  Zhi-Ping Li²  Can Huang²  Sa Yang²  Li Xiang²  Wen Huang²  Peng-Ju Ye²  Qian Ning²  Dong-Xiu He²  Cui-Yun Yu³  Na-Mei Li⁴ 

[1] Chemistry Department, Eastern Kentucky University, Richmond, KY, US;Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China;Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China;Learning Key Laboratory for Pharmacoproteomics of Hunan Province, Institute of Pharmacy & Pharmacology University of South China, Hengyang, China, an;Learning Key Laboratory for Pharmacoproteomics of Hunan Province, Institute of Pharmacy & Pharmacology University of South China, Hengyang, China, an;

关键词: GC-FUA nanoparticles;    5-Fu;    asialoglycoprotein receptor;    drug delivery system;    chitosan;   

DOI  :  10.1080/10717544.2016.1264499

来源: Taylor & Francis

【 摘 要 】

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.

【 授权许可】

CC BY