Amphiphilic polyanhydrides for protein stabilization and release.
Amphiphilic polyanhydrides for protein stabilization and release.
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DOI：
10.1016/j.biomaterials.2006.08.047
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发表时间：
2007
期刊：
影响因子：
14
通讯作者：
M. P. Torres;A. Determan;G. L. Anderson;S. Mallapragada;B. Narasimhan
中科院分区：
文献类型：
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作者：
M. P. Torres;A. Determan;G. L. Anderson;S. Mallapragada;B. Narasimhan
本研究的总体目标是设计基于聚酸酐的新型两亲性生物可降解系统，用于肽和蛋白质的稳定和缓释。因此，已经合成了酸酐、1，6-双（对-羧基苯氧基）己烷（CPH）和1，8-双（对-羧基苯氧基）-3，6-二氧杂辛烷（CPTEG）的共聚物，它们是含单体的低聚乙二醇部分。不同CPTEG：CPH组成的微球已经通过两种非水方法制备：固体/油/油双乳液和低温雾化。这种两亲聚合物体系稳定模型蛋白质的能力（即，溶菌酶和卵清蛋白）。使用凝胶电泳、圆二色性和荧光光谱监测封装的以及释放的蛋白质的结构。发现CPTEG：CPH系统保留了包封蛋白的结构层次。释放的蛋白质的活性研究表明CPTEG：CPH系统保留了释放的蛋白质的生物活性。这些结果是有前途的未来在体内研究，其中涉及新的生物可降解的聚酸酐载体的稳定和持续释放的治疗肽和蛋白质的设计。
The overall goal of this research is to design novel amphiphilic biodegradable systems based on polyanhydrides for the stabilization and sustained release of peptides and proteins. Accordingly, copolymers of the anhydrides, 1,6-bis(p-carboxyphenoxy)hexane (CPH) and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG), which are monomer-containing oligomeric ethylene glycol moieties, have been synthesized. Microspheres of different CPTEG:CPH compositions have been fabricated by two non-aqueous methods: solid/oil/oil double emulsion and cryogenic atomization. The ability of this amphiphilic polymeric system to stabilize model proteins (i.e., lysozyme and ovalbumin) was investigated. The structure of both the encapsulated as well as the released protein was monitored using gel electrophoresis, circular dichroism, and fluorescence spectroscopy. It was found that the CPTEG:CPH system preserves the structural hierarchy of the encapsulated proteins. Activity studies of the released protein indicate the CPTEG:CPH system retains the biological activity of the released protein. These results are promising for future in vivo studies, which involve the design of novel biodegradable polyanhydride carriers for the stabilization and sustained release of therapeutic peptides and proteins.