PLA-microparticles formulated by means a thermoreversible gel able to modify protein encapsulation and release without being co-encapsulated
PLA-microparticles formulated by means a thermoreversible gel able to modify protein encapsulation and release without being co-encapsulated
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DOI：
10.1016/j.ijpharm.2006.05.047
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发表时间：
2006-10-12
影响因子：
5.8
通讯作者：
Vandelli, Maria Angela
中科院分区：
文献类型：
--
作者：
Leo, Eliana;Ruozi, Barbara;Vandelli, Maria Angela
这项工作的目的是开发一种新的策略来制定可生物降解的聚乳酸微球作为蛋白质或肽的递送系统。该策略是基于热可逆Pluronic F127凝胶的凝胶-溶胶过渡的开发。凝胶允许颗粒的形成而不被共困在基质中。用这种新技术制备的微球（TG-Ms，即热可逆凝胶法微球）在体外进行了表征（包括大小、形态、蛋白质包封、释放和蛋白质在聚合物基质中的分布），并与经典的双乳液/溶剂蒸发法制备的微球（w/o/w- ms）进行了比较。采用两种水溶性不同的牛血清白蛋白（BSA）作为模型蛋白。TG-Ms的体积小（7-50 m），蛋白质含量高（8.6%,w/w），与BSA的水溶性无关，而w/o/w- ms的尺寸范围为100-130 μ m，蛋白质含量与BSA的水溶性有关。TG-Ms虽然相对于w/o/w- ms的尺寸较小，但在第二释放阶段表现出较低的初始爆发效应和较高的速率，这导致了一个准恒定的剖面。TG-Ms的释放行为可能是由于蛋白质在颗粒核心的定位（如激光共聚焦扫描显微镜对标记bsa负载的微球的分析所示）和基质中较少的孔隙（如扫描电镜所示）。讨论了粒子形成机制的工作假设。(c) 2006 Elsevier B.V. All。版权。
The aim of this work was to develop a novel strategy for the formulation of biodegradable PLA microspheres as delivery systems for proteins or peptides. The strategy is based on the exploitation of the gel-sol transition of the thermoreversible Pluronic F127 gel. The gel allows the formation of the particles without be co-entrapped in the matrix. The microspheres prepared using the novel technique (TG-Ms, or thermoreversible gel-method microspheres) were characterized in vitro (as concerns the size, the morphology, the protein encapsulation, the release and the protein distribution in the polymer matrix), in comparison with microspheres prepared using the classical double emulsion/solvent evaporation method (w/o/w-Ms). Two types of bovine serum albumin (BSA), with different water solubility, were used as model proteins. TG-Ms exhibited small size (7-50 m) and high protein content (8.6%, w/w) regardless of the BSA water solubility, in contrast with w/o/w-Ms, which revealed a size range of 100-130 mu m and a protein content related to the BSA water solubility. TG-Ms, in spite of their smaller size respect of the w/o/w-Ms, displayed a reduced initial burst effect and a higher rate in the second release phase that resulted in a quasi-constant profile. The release behavior of the TG-Ms may be attributable to both the localization of the protein in the particle core, as shown by the confocal laser scanning microscopy analysis on labeled-BSA loaded microspheres, and the few pores in the matrix, as shown by the scanning electron microscopy. A working hypothesis about the mechanism of the particle formation was also discussed. (c) 2006 Elsevier B.V. All. rights reserved.