National Key Laboratory of Biochemical Engineering, PLA Key Laboratory of Biopharmaceutical Production and Formulation Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
Colloids Surf B Biointerfaces. 2013 Dec 1;112:492-8. doi: 10.1016/j.colsurfb.2013.08.048. Epub 2013 Sep 7.
Exenatide-loaded poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres hold great potential as a drug delivery system to treat type 2 diabetes mellitus (T2DM) because they can overcome the shortcoming of exenatide's short half-life and realize sustained efficacy. However, conventional preparation methods often lead to microspheres with a broad size distribution, which in turn would cause poor preparation repeatability, drug efficacy and so forth. In this study, we used Shirasu Porous Glass (SPG) premix membrane emulsification technique characterized with high trans-membrane flux and size controllability to prepare uniform-sized PLGA microspheres. By optimizing trans-membrane pressure and PVA concentration in external aqueous phase, uniform-sized PLGA microspheres with large size (around 20μm) were successfully obtained. To achieve high encapsulation efficiency (EE) and improve in vitro release behavior, we have carefully examined the process parameters. Our results show that using ultrasonication to form primary emulsion, microspheres with high EE were easily obtained, but the rate of in vitro release was very slow. Instead, high EE and appropriate in vitro release were achieved when homogenization with optimized time and speed were employed. Besides, we also systematically investigated the effect of formulations on loading efficiency (LE) as well as the relationship between the resultant size of the microspheres and pore size of the membrane. Finally, through RP-HPLC and CD spectra analysis, we have demonstrated that the bio-stability of exenatide in microspheres was preserved during the preparation process.
载有艾塞那肽的聚（丙交酯-乙交酯）（PLGA）微球作为治疗 2 型糖尿病（T2DM）的药物传递系统具有很大的潜力，因为它们可以克服艾塞那肽半衰期短的缺点，实现持续的疗效。然而，传统的制备方法往往会导致微球的粒径分布较宽，从而导致制备重复性差、药效不佳等问题。在本研究中，我们使用具有高通量和尺寸可控性的 Shirasu 多孔玻璃（SPG）预混膜乳化技术制备均匀粒径的 PLGA 微球。通过优化跨膜压力和外部水相中的 PVA 浓度，成功制备出粒径较大（约 20μm）的均匀粒径的 PLGA 微球。为了实现高包封率（EE）和改善体外释放行为，我们仔细研究了工艺参数。结果表明，采用超声形成初级乳液，可获得高 EE 的微球，但体外释放速率非常缓慢。相反，当采用优化时间和速度的匀浆化处理时，可获得高 EE 和适当的体外释放。此外，我们还系统地研究了制剂对载药量（LE）的影响以及微球的粒径与膜孔大小之间的关系。最后，通过 RP-HPLC 和 CD 光谱分析，我们证明了艾塞那肽在微球中的生物稳定性在制备过程中得以保持。
