Preparing polymer-based sustained-release systems without exposing proteins to water-oil or water-air interfaces and cross-linking reagents
Preparing polymer-based sustained-release systems without exposing proteins to water-oil or water-air interfaces and cross-linking reagents
复制标题
制备基于聚合物的缓释系统，无需将蛋白质暴露于水-油或水-空气界面和交联试剂
DOI：
10.1016/j.jconrel.2008.02.010
复制
发表时间：
2008-05-22
影响因子：
10.8
通讯作者：
Zhu, Hua
中科院分区：
文献类型：
--
作者：
Jin, Tuo;Zhu, Hahao;Zhu, Hua
我们报告了一种将蛋白质装载到基于聚合物的缓释系统中而不将其暴露于水-油或水-空气界面的方法，这些界面是已知的使蛋白质变性的因素。通过将含有蛋白质的葡聚糖溶液分散到含有少量藻酸盐的PEG溶液中，形成稳定的水-水“乳液”。聚阴离子藻酸盐在每个葡聚糖液滴周围产生扩散双层，以防止它们彼此接触并融合成封闭相。蛋白质通过有利于右旋糖酐的优先分配分布在稳定的右旋糖酐液滴中。冷冻干燥该乳液得到负载蛋白质的葡聚糖颗粒，直径为1-2 μ m，密度为1.6 g/cm（3）。通过使用有机溶剂洗涤冻干粉末以除去PEG连续相来收获颗粒。包封的β-半乳糖苷酶的活性测定表明，蛋白质活性在颗粒形成过程中得到保留，包括在有机溶剂中超声处理颗粒的步骤。当包封在可降解聚合物缓释系统中时，葡聚糖颗粒还改善了蛋白质的释放曲线和完整性。水-水乳液提供了制备耐溶剂蛋白质-多糖颗粒的方便方法，所述颗粒可以容易地掺入各种基于聚合物的药物剂型和医疗装置中，例如用于持续释放蛋白质递送的微球、支架和药物洗脱支架。(C)2008 Elsevier B. V.保留所有权利。
We report a method to load proteins into polymer-based sustained-release systems without exposing them to water-oil or water-air interfaces, factors known to denature proteins. By dispersing a dextan solution containing a protein into a PEG solution containing small amount of alginate, a stable aqueous-aqueous "emulsion" was formed. The poly-anionic alginate generated a diffuse double layer around each dextran droplet to prevent them from contacting with each other and fusing to a block phase. Proteins distributed in the stabilized dextran droplets by preferential partition favoring dextran. Freeze-drying this emulsion resulted in protein-loaded dextran particles, 1-2 mu m in diameter and 1.6 g/cm(3) in density. The particles were harvested by washing the lyophilized powder using organic solvents to remove the PEG continuous phase. An activity assay of encapsulated P-galactosidase indicated that protein activity was preserved during the particle-forming process including the step of sonicating the particles in organic solvents. The dextran particles also improved release profile and integrity of proteins when encapsulated in degradable polymer sustained-release systems. The aqueous-aqueous emulsion offers a convenient way to prepare solvent-resistant protein-polysaccharide particles that can easily be incorporated in a variety of polymer-based pharmaceutical dosage forms and medical devices such as microspheres, scaffolds and drug-eluting stents for sustained-release protein delivery. (C) 2008 Elsevier B.V. All rights reserved.