Liver-targeting doxorubicin-conjugated polymeric prodrug with pH-triggered drug release profile

被引：28

作者：

Huang, Jin ^{[1
,2
]}

Gao, Feng ^{[1
]}

Tang, Xiaoxin ^{[1
]}

Yu, Jiahui ^{[1
]}

Wang, Daxin ^{[3
]}

Liu, Shiyuan ^{[4
]}

Li, Yaping ^{[5
]}

机构：

[1] E China Normal Univ, Inst Adv Interdisciplinary Res, Shanghai 200062, Peoples R China

[2] Wuhan Univ Technol, Coll Chem Engn, Wuhan 430070, Peoples R China

[3] Yangzhou Univ, Subei Hosp Jiangsu Prov, Yangzhou 225001, Peoples R China

[4] Changzheng Hosp, Dept Diagnost Imaging, Shanghai 200003, Peoples R China

[5] Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Delivery Syst, Shanghai 201203, Peoples R China

来源：

POLYMER INTERNATIONAL | 2010年 / 59卷 / 10期

关键词：

Gal-PEG-b-PAMAM-Dox(n); polymeric prodrug; pH-triggered drug release; doxorubicin; liver-targeting; DELIVERY; DENDRIMERS; CYTOTOXICITY; COPOLYMER; MECHANISM; PAMAM; MICE;

D O I：

10.1002/pi.2880

中图分类号：

O63 [高分子化学（高聚物）];

学科分类号：

070305 ; 080501 ; 081704 ;

摘要：

The aim of the research presented was to develop a potential liver-targeting prolonged-circulation polymeric prodrug of doxorubicin (Dox) with a pH-triggered drug release profile. In particular, linear dendritic block copolymers composed of polyamidoamine dendrimer (PAMAM) and poly(ethylene glycol) (PEG; number-average molecular weight of 2000 g mol(-1)) with or without galactose (Gal) were synthesized. Dox was coupled to the copolymers via an acid-labile hydrazone linker. These prodrugs, designated Gal-PEG-b-PAMAM-Dox(n) and mPEG-b-PAMAM-Dox(m), showed accelerated Dox release as the pH decreased from 8.0 to 5.6. Cytotoxicity of the prodrugs was lower than that of free Dox due to the gradual drug release nature. Compared to mPEG-b-PAMAM-Dox(m), Gal-PEG-b-PAMAM-Dox(n) showed rather high cytotoxicity against Bel-7402, suggestive of its galactose receptor-mediated enhanced tumor uptake. This galactose receptor-mediated liver-targeted profile was further confirmed by the prolonged retention time in hepatoma tissue monitored using magnetic resonance imaging. Gal-PEG-b-PAMAM-Dox(n) showed better in vivo antitumor efficacy than free Dox, suggesting its great potential as a polymeric antitumor prodrug. (C) 2010 Society of Chemical Industry

引用

页码：1390 / 1396

页数：7