Qi Feng, Wu Jie, Yang Tingyuan, Ma Guanghui, Su Zhiguo
State Key Laboratory of Biochemical Engineering, PLA Key Laboratory of Biopharmaceutical Production & Formulation Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, People's Republic of China; University of the Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
State Key Laboratory of Biochemical Engineering, PLA Key Laboratory of Biopharmaceutical Production & Formulation Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.
Acta Biomater. 2014 Oct;10(10):4247-56. doi: 10.1016/j.actbio.2014.06.018. Epub 2014 Jun 18.
Poly(DL-lactic-co-glycolic acid) (PLGA) microspheres have been widely prepared by many methods, including solvent evaporation, solvent extraction and the co-solvent method. However, very few studies have compared the properties of microspheres fabricated by these methods. This is partly because the broad size distribution of the resultant particles severely complicates the analysis and affects the reliability of the comparison. To this end, uniform-sized PLGA microspheres have been prepared by Shirasu porous glass premix membrane emulsification and used to encapsulate exenatide, a drug for treating Type 2 diabetes. Based on this technique, the influences on the properties of microspheres fabricated by the aforementioned three methods were intensively investigated, including in vitro release, degradation and pharmacology. We found that these microspheres presented totally different release behaviors in vitro and in vivo, but exhibited a similar trend of PLGA degradation. Moreover, the internal structural evolution visually demonstrated these release behaviors. We selected for further examination the microsphere prepared by solvent evaporation because of its constant release rate, and explored its pharmacodynamics, histology, etc., in more detail. This microsphere when injected once showed equivalent efficacy to that of twice-daily injections of exenatide with no inflammatory response.
聚（DL-乳酸-乙醇酸）（PLGA）微球已通过多种方法广泛制备，包括溶剂蒸发法、溶剂萃取法和共溶剂法。然而，很少有研究比较通过这些方法制备的微球的性质。部分原因是所得颗粒的宽泛尺寸分布严重使分析复杂化并影响比较的可靠性。为此，通过白榴石多孔玻璃预混膜乳化法制备了尺寸均匀的PLGA微球，并用于包封艾塞那肽（一种治疗2型糖尿病的药物）。基于该技术，深入研究了上述三种方法对制备的微球性质的影响，包括体外释放、降解和药理学。我们发现这些微球在体外和体内呈现出完全不同的释放行为，但表现出相似的PLGA降解趋势。此外，内部结构演变直观地证明了这些释放行为。由于其恒定的释放速率，我们选择对通过溶剂蒸发法制备的微球进行进一步研究，并更详细地探索其药效学、组织学等。这种微球单次注射显示出与每日两次注射艾塞那肽等效的疗效，且无炎症反应。
