Synthesis and characterization of a novel polydepsipeptide contained tri-block copolymer (mPEG-PLLA-PMMD) as self-assembly micelle delivery system for paclitaxel

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• 作者：Yanlei Zhao^a ; ¹ ; Juan Li^a ; ¹ ; ^{lijuancpu@163.com} ; Hua Yu^c ; Guangji Wang^b ; ^{guangjiwang@hotmail.com} ; Wen Liu^a
• 关键词：Polydepsipeptide ; Amphiphilic block copolymer ; Paclitaxel ; Self-assembly ; Long-circulation ; Cytotoxicity
• 刊名：International Journal of Pharmaceutics
• 出版年：2012
• 期刊代码：24_03785173
• 类别：pha
• 出版时间：1 July, 2012
• 卷：430
• 期：1-2
• 页码：282-291
• 文件大小：1084 K

摘要

A series of biodegradable polydepsipeptides based new triblock copolymers, poly (ethylene glycol)-poly(l-lactide)-poly(3(S)-methyl-morpholine-2,5-dione) (mPEG-PLLA-PMMD) have been synthesized and characterized as self-assembly micelle delivery system for paclitaxel (PTX). Compared to the mPEG₂₀₀₀-PLLA₂₀₀₀ diblock copolymers, the triblock copolymers present more benefits such as lower CMC value, positive-shifted zeta potential, better drug loading efficiency and stability. Among the triblock polymers, mPEG₂₀₀₀-PLLA₂₀₀₀-PMMD₁₄₀₀ micelles present low cytotoxicity and promote the anti-cancer activity of PTX on A-549 and HCT-116 cells. In addition, mPEG₂₀₀₀-PLLA₂₀₀₀-PMMD₁₄₀₀ micelles prolongs the circulation time of PTX in rat after i.v. injection (5 mg/kg) than that of mPEG₂₀₀₀-PLLA₂₀₀₀ micelles and Taxol^庐. The half life (t_1/2尾), mean residence time (MRT), AUC_{0-鈭?/sub> and clearance (CL) for PTX-loaded mPEG2000-PLLA2000-PMMD1400 micelles are determined to be 1.941 h, 2.683 h, 5.220 渭g/mL h (1.8-fold to mPEG2000-PLLA2000 group), 0.967 L/h kg^鈭?, respectively. In conclusion, mPEG2000-PLLA2000-PMMD1400 copolymer could be developed as one of the promising vectors to anti-cancer agents for chemotherapeutics.}