Preparation of uniform-sized exenatide-loaded PLGA microspheres as long-effective release system with high encapsulation efficiency and bio-stability
Preparation of uniform-sized exenatide-loaded PLGA microspheres as long-effective release system with high encapsulation efficiency and bio-stability
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DOI：
10.1016/j.colsurfb.2013.08.048
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发表时间：
2013-12-01
影响因子：
5.8
通讯作者：
Su, Zhiguo
中科院分区：
文献类型：
--
作者：
Qi, Feng;Wu, Jie;Su, Zhiguo
艾塞那肽聚乳酸-羟基乙酸共聚物（PLGA）微球由于能克服艾塞那肽半衰期短的缺点，实现持续疗效，因此有望成为治疗2型糖尿病（T2 DM）的药物载体。然而，传统的制备方法往往导致微球的粒径分布较宽，这反过来又会导致制备重复性差，药效不佳等。本研究采用具有高膜通量和粒径可控性的Shirasu多孔玻璃（SPG）预混膜乳化技术制备了粒径均匀的PLGA微球。通过优化跨膜压差和外水相中PVA浓度，成功地获得了粒径较大（约20 μ m）、大小均匀的PLGA微球。为了实现高包封率（EE）和改善体外释放行为，我们仔细检查了工艺参数。结果表明，超声乳化法制备的微球具有较高的包封率，但其体外释药速度较慢。相反，当采用优化时间和速度的均质化时，实现了高EE和适当的体外释放。此外，我们还系统地研究了配方对负载效率（LE）的影响以及所得微球尺寸与膜孔径之间的关系。最后，通过RP-HPLC和CD光谱分析，证明艾塞那肽微球在制备过程中保持了生物稳定性。(C)2013爱思唯尔有限公司版权所有。
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 20 mu m) 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. (C) 2013 Elsevier B.V. All rights reserved.