Poly(lactide-co-glycolide) (PLGA) copolymers were synthesized by ring opening polymerization in presence of zinc proline and stannous octoate in bulk through green route and were designated as PLGA-1 and PLGA-2 respectively. These copolymers were characterized using NMR, SEC, DSC, X-ray and MALDI-TOF analysis. For the first time, the low molecular weight of PLGA (~11,000 Da) was mainly targeted to explore acute oral toxicity in the presence of zinc L-proline and stannous octoate. The haemolysis and cell viability assay were carried out for in-vitro cytotoxicity assessment. Haemolysis assay of PLGA-2 was confirmed and haemolytic potential exceeded limit of American society of testing of material standard. The cell viability study using fibroblast cell lines (NIH3T3), exhibited statistically significant difference in results between PLGA-1 and PLGA-2. The acute toxicity study was performed in Balb/c mice for biomarker, hematological and histopathological analysis. No mortality was observed during the entire observation period, and no macroscopic change of the organs was observed in PLGA-1 treated group where PLGA-2 treated group showed sign of toxicity. The results obtained from in-vitro and in-vivo studies suggested that PLGA-2 was toxic whereas PLGA-1 was nontoxic in nature. Therefore, PLGA-1 can be regarded as biocompatible biomaterials for potential for drug delivery and biomedical application.

中文翻译：

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使用L-脯氨酸锌通过生物医学应用的绿色途径合成低分子量PLGA共聚物的生物相容性评价

聚（丙交酯-共-乙交酯）（PLGA）共聚物在脯氨酸锌和辛酸亚锡的存在下通过绿色路线开环聚合合成，分别命名为PLGA-1和PLGA-2。使用NMR、SEC、DSC、X-射线和MALDI-TOF分析表征这些共聚物。PLGA 的低分子量（~11,000 Da）首次主要用于探索在 L-脯氨酸锌和辛酸亚锡存在下的急性口服毒性。进行溶血和细胞活力测定以进行体外细胞毒性评估。PLGA-2的溶血试验得到证实，溶血潜力超过美国物质检测协会标准的限值。使用成纤维细胞系 (NIH3T3) 进行的细胞活力研究，PLGA-1 和 PLGA-2 之间的结果显示出统计学上的显着差异。急性毒性研究在 Balb/c 小鼠中进行，用于生物标志物、血液学和组织病理学分析。在整个观察期内没有观察到死亡，在 PLGA-1 治疗组中没有观察到器官的宏观变化，其中 PLGA-2 治疗组显示出毒性迹象。从体外和体内研究获得的结果表明 PLGA-2 是有毒的，而 PLGA-1 本质上是无毒的。因此，PLGA-1 可被视为具有潜在药物递送和生物医学应用的生物相容性生物材料。在PLGA-1治疗组中未观察到器官的宏观变化，其中PLGA-2治疗组显示出毒性迹象。从体外和体内研究获得的结果表明 PLGA-2 是有毒的，而 PLGA-1 本质上是无毒的。因此，PLGA-1 可被视为具有潜在药物递送和生物医学应用的生物相容性生物材料。在PLGA-1治疗组中未观察到器官的宏观变化，其中PLGA-2治疗组显示出毒性迹象。从体外和体内研究获得的结果表明 PLGA-2 是有毒的，而 PLGA-1 本质上是无毒的。因此，PLGA-1 可被视为具有潜在药物递送和生物医学应用的生物相容性生物材料。