Development and characterization of cores-shell poly(lactide-co-glycolide)-chitosan microparticles for sustained release of GDNF
Development and characterization of cores-shell poly(lactide-co-glycolide)-chitosan microparticles for sustained release of GDNF
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用于持续释放 GDNF 的核壳聚丙交酯-乙交酯-壳聚糖微粒的开发和表征
DOI：
10.1016/j.colsurfb.2017.08.052
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发表时间：
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期刊：
影响因子：
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通讯作者：
Guodong Gao
中科院分区：
文献类型：
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作者：
Wen Zeng;Zhongyang Liu;Yuqian Li;Shu Zhu;Jie M;Weixin Li;Guodong Gao
生物可降解聚乳酸-羟基乙酸共聚物（PLGA）微球微囊化生物活性神经营养因子已成为治疗各种神经系统疾病的一种有前途的工具。然而，挑战仍然存在; PLGA的突发药物释放和酸性降解产物往往限制了临床应用。本研究采用再乳化法制备了壳聚糖单壳层和PLGA多核层的核壳型PLGA-壳聚糖微球。胶质细胞源性神经营养因子（GDNF）被包裹在核-壳MP的PLGA核中。不同壳聚糖浓度制备的核壳型微球表面粗糙，平均粒径在32.3 ~ 45.2 μm之间。荧光图像显示，尼罗红染色的PLGA微球均匀分布在核-壳型MP中。与PLGA微球相比，壳-核MPs能够降低GDNF的初始突释，并中和PLGA降解产物的酸性，这一作用可通过改变壳聚糖浓度来调节。体外PC 12细胞向神经元型分化的实验结果表明，核壳结构的MPs在制备过程中能够保持GDNF的生物活性。总之，这些发现突出了使用核-壳PLGA-壳聚糖MP用于持续释放GDNF的可能性，其在神经损伤修复中提供了潜在的应用。
The microencapsulation of bioactive neurotrophic factors in biodegradable poly(lactide-co-glycolide) (PLGA) microspheres has been a promising tool in the treatment of various nervous system disorders. However, challenges still exist; the PLGA burst drug release and acidic degradation products often limit clinical application. In this study, cores–shell PLGA-chitosan microparticles (MPs) were fabricated with a single shell of chitosan and multi-cores of PLGA using a re-emulsification method. The glial cell line-derived neurotrophic factor (GDNF) was encapsulated at the PLGA cores of the cores–shell MPs. The cores–shell MPs prepared by different chitosan concentrations showed a rough surface, and the particle mean size varied between 32.3 and 45.2 μm. The fluorescence images indicated that Nile red-stained PLGA microspheres were uniformly distributed in the cores–shell MPs. Compared with PLGA microspheres, the cores–shell MPs were able to reduce the initial burst release of GDNF and neutralize the acidity of PLGA degradation products, which could be modulated by changing the chitosan concentrations. Further differentiation of PC12 cells toward a neuronal phenotypein vitroindicated that the cores–shell MPs were capable of maintaining the bioactivity of GDNF during preparation. Taken together, these findings highlight the possibility of using cores–shell PLGA-chitosan MPs for the sustained release of GDNF, which offers potential applications in nerve injury repair.