Synthesis and characterization of multi-functional linear-dendritic block copolymer for intracellular delivery of antitumor drugs

被引：19
作者：
Qiao, Hongzhi [1 ]
Li, Juan [1 ]
Wang, Yang [1 ]
Ping, Qineng [1 ]
Wang, Guangji [2 ]
Gu, Xiaochen [3 ]
机构：
[1] China Pharmaceut Univ, Dept Pharmaceut, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
[2] China Pharmaceut Univ, Ctr Pharmacokinet, Key Lab Drug Metab & Pharmacokinet, Nanjing 210009, Jiangsu, Peoples R China
[3] Univ Manitoba, Fac Pharm, Winnipeg, MB R3E 0T5, Canada
来源：
INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2013年 / 452卷 / 1-2期
关键词：
Linear-dendritic block copolymers; pH-sensitive; Specific drug targeting; Cellular uptake; Pharmacokinetics; IN-VIVO EVALUATION; PAMAM DENDRIMERS; BIOMEDICAL APPLICATIONS; SOLID TUMORS; MICELLES; VITRO; POLY(AMIDOAMINE); DOCETAXEL; PHARMACOKINETICS; NANOPARTICLES;
D O I：
10.1016/j.ijpharm.2013.05.003
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
A novel amphiphilic linear-dendritic block copolymer, semi-polyamidoamine-b-poly(D,L-lactic acid) (PALA) was synthesized and evaluated for its potential as a drug delivery system in this study. PALA was self-assembled in aqueous solution to form nanomicelles with low critical micelle concentration; antitumor drug docetaxel (DTX) was successfully encapsulated into micelles. The prepared micelles demonstrated pH-induced charge conversion and dimension changes. In vitro drug release suggested susceptibility of DTX-loaded micelles to acidic microenvironment. Hemolysis and cytotoxicity testing also indicated in vitro biocompatibility of PALA. Pharmacokinetic study in rats proved that DTX-loaded PALA micelles enhanced the AUC of DTX and prolonged drug clearance in comparison to conventional DTX injection (Taxotere (R)). It was concluded that self-assembled micelles from linear-dendritic block copolymer PALA demonstrated potential for intracellular delivery of anticancer molecules, and that its safety and efficacy in chemotherapy should be further studied. (C) 2013 Elsevier B. V. All rights reserved.
引用
收藏
页码：363 / 373
页数：11
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