Wang Chenhui, Yu Changhui, Yu Kongtong, Teng Lesheng, Liu Jiaxin, Wang Xuesong, Sun Fengying, Li Youxin
School of Life Sciences, Jilin University, Changchun 130012, China.
Curr Drug Deliv. 2015;12(6):726-35. doi: 10.2174/1567201812666150316112635.
The use of biodegradable polymers such as PLGA to encapsulate therapeutic proteins for their controlled release has received tremendous interest. However, an acidic environment caused by PLGA degradation productions leads to protein incomplete release and chemical degradation. The aim of this study was to develop novel PCADK/PLGA microspheres to improve protein stability and release behavior. Bovine serum albumin (BSA) incubated in PCADK and PLGA degradation products was investigated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), size exclusion chromatography (SEC-HPLC), circular dichroism (CD) and fluorescence spectroscopy. Blended microspheres of PCADK/PLGA were prepared in different ratios and the release behaviors of the microspheres and the protein stability were then measured. The degradation properties of the microspheres and the pH inside the microspheres were systematically investigated by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) to examine the mechanism of autocatalytic degradation and protein stability. BSA was more stable in the presence of PCADK monomers than it was in the presence of PLGA monomers, revealing that PCADK is highly compatible with this protein. PCADK/PLGA microspheres were successfully prepared, and 2/8 was determined to be the optimal ratio. Further, 43% of the BSA formed water-insoluble aggregates in the presence of PCADK/PLGA microspheres, compared with 57% for the PLGA microspheres, demonstrating that the BSA encapsulated in PCADK/PLGA blended microspheres was more stable than in PLGA microspheres. The PCADK/PLGA blended microspheres improved protein stability and release behavior, providing a promising protein drug delivery system.
使用聚乳酸-羟基乙酸共聚物（PLGA）等可生物降解聚合物来封装治疗性蛋白质以实现其控释已引起了极大的关注。然而，PLGA降解产物导致的酸性环境会致使蛋白质不完全释放以及化学降解。本研究的目的是开发新型的聚（2-羧乙基丙烯酸酯-co-癸二酸-co-己内酯）/聚乳酸-羟基乙酸共聚物（PCADK/PLGA）微球，以提高蛋白质的稳定性和释放行为。使用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）、尺寸排阻色谱（SEC-HPLC）、圆二色性（CD）和荧光光谱法研究了在PCADK和PLGA降解产物中孵育的牛血清白蛋白（BSA）。制备了不同比例的PCADK/PLGA混合微球，然后测量了微球的释放行为和蛋白质稳定性。通过扫描电子显微镜（SEM）和共聚焦激光扫描显微镜（CLSM）系统地研究了微球的降解特性和微球内部的pH值，以探究自催化降解机制和蛋白质稳定性。与在PLGA单体存在下相比，BSA在PCADK单体存在下更稳定，这表明PCADK与这种蛋白质具有高度相容性。成功制备了PCADK/PLGA微球，并确定2/8为最佳比例。此外，在PCADK/PLGA微球存在下，43%的BSA形成了水不溶性聚集体，而PLGA微球为57%，这表明封装在PCADK/PLGA混合微球中的BSA比在PLGA微球中更稳定。PCADK/PLGA混合微球改善了蛋白质的稳定性和释放行为，提供了一种有前景的蛋白质药物递送系统。
