Improved stability and tumor targeting of 5-fluorouracil by conjugation with hyaluronan

被引：31

作者：

Dong, Zhikui ^{[1
]}

Zheng, Wenyi ^{[1
]}

Xu, Zaiyang ^{[1
]}

Yin, Zongning ^{[1
]}

机构：

[1] Sichuan Univ, Key Lab Drug Targeting & Drug Delivery Syst, West China Sch Pharm, Chengdu 610041, Peoples R China

来源：

JOURNAL OF APPLIED POLYMER SCIENCE | 2013年 / 130卷 / 02期

基金：

中国国家自然科学基金;

关键词：

drug delivery systems; synthesis and processing; polysaccharides; CANCER; MECHANISM; PRODRUGS; DESIGN;

D O I：

10.1002/app.39247

中图分类号：

O63 [高分子化学（高聚物）];

学科分类号：

070305 ; 080501 ; 081704 ;

摘要：

To circumvent the rapid clearance in vivo and consequent low tumor targeting of 5-fluorouracil (5-Fu), hyaluronan-5-fluorouracil conjugate (HA-5-Fu) was firstly synthesized and characterized. in vitro was evaluated by incubation with phosphate buffered saline, hyaluronidase solution, and mice plasma, respectively. in vitro cytotoxicity evaluation and in vivo pharmacokinetics study in plasma and tumor. HA-5-Fu with drug loading of 87.674 mg/g was successfully obtained and confirmed. HA-5-Fu showed high stability in acidic environment and moderate stability under enzymatic cleavage. t(1/2) of HA-5-Fu in plasma after injection of prodrug was extended up to 10 times compared with that of 5-Fu. Notably, AUC(0-t) in tumors of HA-5-Fu was 3.6 times higher than 5-Fu, demonstrating its excellent tumor targeting and quite promising prospect in anti-cancer therapy. (c) 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 927-932, 2013

引用

页码：927 / 932

页数：6

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