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

被引：26

作者：

Huang, Can ^{[1
]}

Li, Na-Mei ^{[2
]}

Gao, Pei ^{[3
]}

Yang, Sa ^{[1
]}

Ning, Qian ^{[1
]}

Huang, Wen ^{[1
]}

Li, Zhi-Ping ^{[1
]}

Ye, Peng-Ju ^{[1
]}

Xiang, Li ^{[1
]}

He, Dong-Xiu ^{[1
]}

Tan, Xiang-Wen ^{[1
]}

Yu, Cui-Yun ^{[1
,2
]}

机构：

[1] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China

[2] Univ South China, Inst Pharm & Pharmacol, Learning Key Lab Pharmacoprote Hunan Prov, Hengyang, Peoples R China

[3] Eastern Kentucky Univ, Dept Chem, Richmond, KY 40475 USA

来源：

DRUG DELIVERY | 2017年 / 24卷 / 01期

基金：

中国国家自然科学基金;

关键词：

GC-FUA nanoparticles; 5-Fu; asialoglycoprotein receptor; drug delivery system; chitosan; CHITOSAN NANOPARTICLES; GALACTOSYLATED CHITOSAN; DRUG; DELIVERY; 5-FLUOROURACIL; CANCER; SYSTEMS;

D O I：

10.1080/10717544.2016.1264499

中图分类号：

R9 [药学];

学科分类号：

1007 ;

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.

引用

页码：459 / 466

页数：8

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