Triblock copolymers: synthesis, characterization, and delivery of a model protein
Triblock copolymers: synthesis, characterization, and delivery of a model protein
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DOI：
10.1016/j.ijpharm.2004.09.026
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发表时间：
2005-01-20
影响因子：
5.8
通讯作者：
Singh, J
中科院分区：
文献类型：
--
作者：
Chen, SB;Pieper, R;Singh, J
本研究的目的是合成和表征生物可降解和热敏性三嵌段共聚物，用于以生物活性形式以受控速率递送蛋白质，持续时间更长。以聚乙二醇（PEG）为引发剂，通过D，L-丙交酯和乙交酯的开环聚合，合成了一系列不同嵌段长度的温敏性三嵌段共聚物（PLGA-PEG-PLGA）。用核磁共振氢谱和凝胶渗透色谱分别表征了三嵌段共聚物的组成和分子量。采用单管倒置法测定了溶胶-凝胶转变温度。溶菌酶被用作模型蛋白。用不同的三嵌段共聚物制备溶菌酶溶液制剂用于体外释放。释放样品中的溶菌酶浓度及其生物活性分别使用标准MicroBCA法和细菌细胞裂解法测定。考察了不同嵌段长度和共聚物浓度对溶菌酶体外释放的影响。制剂的释放曲线显示较高的初始释放，随后缓慢释放长达4周。增加共聚物的嵌段长度使溶菌酶的突释从41.2 +/- 5.4%降低到16.1 +/-3.9%。增加共聚物浓度降低药物释放。溶菌酶在4周释放样品中保留了其大部分生物活性（>80%）。通过改变三嵌段共聚物的嵌段长度和浓度，以生物活性形式递送蛋白质持续更长的时间是可行的。(C)2004 Elsevier B. V.保留所有权利。
The purpose of this study was to synthesize and characterize biodegradable and thermosensitive triblock copolymers for delivering protein at controlled rate in biologically active form for longer duration of time. A series of thermosensitive triblock copolymers with different block lengths (PLGA-PEG-PLGA) were synthesized by ring-opening polymerization of D,L-lactide and glycolide with polyethylene glycol (PEG) in the presence of stannous octoate. Compositions and molecular weight of triblock copolymers were characterized by H-1 NMR spectrometry and gel permeation chromatography, respectively. A single test-tube inverting method was employed to determine the sol-gel transition temperature. Lysozyme was used as a model protein. Lysozyme solution formulation was prepared with different triblock copolymers for in vitro release. Lysozyme concentration and its biological activity in the released sample were determined using a standard MicroBCA method and bacterial cell lysis method, respectively. The effects of varying block lengths and concentrations of copolymers on the in vitro release of lysozyme were evaluated. The release profiles from formulations showed a higher initial release followed by slower release up to 4 weeks. Increasing the block lengths of copolymers decreased burst release of lysozyme from 41.2 +/- 5.4% to 16.1 +/- 3.9%. Increasing copolymer concentrations decreased the drug release. Lysozyme in the 4 weeks released samples retained most of its biological activity (>80%). It is feasible to deliver protein in biologically active form for longer duration by varying block lengths and concentrations of triblock copolymers. (C) 2004 Elsevier B.V. All rights reserved.