Blanco D, Alonso M J
University of Santiago de Compostela, Spain.
Eur J Pharm Biopharm. 1998 May;45(3):285-94. doi: 10.1016/s0939-6411(98)00011-3.
Despite the recognised role of the poly(lactide-co-glycolide) (PLGA) in the encapsulation and release of proteins from PLGA microspheres, the importance that the characteristics of the protein have in these processes has not yet been sufficiently investigated. The aim of this work was to study the simultaneous effect of the protein and PLGA properties and of the microencapsulation process on the physicochemical and in vitro release characteristics of protein-loaded PLGA microspheres. Two model proteins of different isoelectric points (pI), bovine serum albumin (BSA) (pI = 4.6) and lysozyme (LZM) (pI = 11.2), and two different molecular weights (Mw) of PLGA were selected. Microspheres were prepared using the water-in-oil-in-water (w/o/w) solvent extraction and the oil-in-oil (o/o) solvent evaporation techniques. Results showed that BSA was efficiently encapsulated independent of the PLGA Mw, whereas the encapsulation of LZM was favoured with the low Mw PLGA. The co-encapsulation of a surfactant (poloxamer 188 or 331) reduced the protein encapsulation efficiency, especially of BSA. These results suggested that the tensoactive properties of the protein and its affinity for the PLGA are major determinants of the protein encapsulation. Both proteins released faster from the microspheres prepared by the o/o solvent evaporation procedure, with respect to those prepared by the w/o/w solvent extraction technique. In addition, both polymer Mw and protein type had an effect on the protein release rate. The release rate of both proteins, in the absence of a surfactant, was faster from the low Mw PLGA microspheres. However, the release rate constant was higher for BSA than for LZM irrespective of the PLGA Mw. In addition, the co-encapsulation of a surfactant led, in most cases, to a faster release of the encapsulated protein. To conclude, these results suggest that protein release from PLGA microspheres is not only governed by the PLGA erosion rate and protein diffusion through the water-filled channels, but is highly affected by the protein properties and its possible interaction with PLGA and its degradation products.
尽管聚（丙交酯-共-乙交酯）（PLGA）在从PLGA微球中包封和释放蛋白质方面的作用已得到认可，但蛋白质特性在这些过程中的重要性尚未得到充分研究。这项工作的目的是研究蛋白质和PLGA特性以及微囊化过程对载蛋白PLGA微球的物理化学和体外释放特性的同时影响。选择了两种不同等电点（pI）的模型蛋白，牛血清白蛋白（BSA）（pI = 4.6）和溶菌酶（LZM）（pI = 11.2），以及两种不同分子量（Mw）的PLGA。使用水包油包水（w/o/w）溶剂萃取和油包油（o/o）溶剂蒸发技术制备微球。结果表明，BSA的有效包封与PLGA的Mw无关，而低Mw的PLGA有利于LZM的包封。表面活性剂（泊洛沙姆188或331）的共包封降低了蛋白质包封效率，尤其是BSA的包封效率。这些结果表明，蛋白质的表面活性特性及其对PLGA的亲和力是蛋白质包封的主要决定因素。相对于通过w/o/w溶剂萃取技术制备的微球，两种蛋白质从通过o/o溶剂蒸发程序制备的微球中释放得更快。此外，聚合物Mw和蛋白质类型都对蛋白质释放速率有影响。在没有表面活性剂的情况下，两种蛋白质从低Mw PLGA微球中的释放速率更快。然而，无论PLGA的Mw如何，BSA的释放速率常数都高于LZM。此外，表面活性剂的共包封在大多数情况下导致包封蛋白质的更快释放。总之，这些结果表明，蛋白质从PLGA微球中的释放不仅受PLGA侵蚀速率和蛋白质通过充满水的通道扩散的控制，而且还受到蛋白质特性及其与PLGA及其降解产物可能相互作用的高度影响。
