University Institute of Pharmaceutical Sciences (UGC Centre of Advanced Studies), Panjab University, Chandigarh, India.
J Biomater Appl. 2011 Mar;25(7):699-720. doi: 10.1177/0885328209359959. Epub 2010 Mar 5.
Phase-sensitive in situ gel-forming controlled release formulations of insulin were prepared using poly(lactide-co-glycolide) and a solvent system consisting of various proportions of benzyl benzoate and benzyl alcohol. The in vitro release samples of formulations were assayed for insulin content by enzyme linked immunosorbent assay. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and circular dichroism spectroscopy studies of released insulin confirmed its conformational stability. The stability of insulin in the formulation was assessed using Fourier transform infrared spectroscopy. Rheological properties of the formulations, assessed under isothermal conditions, showed dilatant behavior of all the formulations. In vivo studies were carried out on the optimized formulations vis-à-vis pure insulin in mice and blood glucose levels were monitored for 15 days. Mean percentage reduction in blood glucose levels was calculated in all the animals and the results analyzed using ANOVA. The studies construed better pharmacodynamic response for the two optimized formulations in controlling the blood glucose levels vis-à-vis routine once-a-day administration of insulin. The subcutaneous tissues, further subjected to scanning electron microscopy studies and histopathological examinations, ascertained the biocompatibility of the formulation.
采用聚（乳酸-共-乙醇酸）和由不同比例苄基苯甲酸酯和苄醇组成的溶剂系统，制备了胰岛素的相敏原位凝胶形成控释制剂。通过酶联免疫吸附试验测定制剂的体外释放样品中的胰岛素含量。释放胰岛素的十二烷基硫酸钠聚丙烯酰胺凝胶电泳和圆二色性光谱研究证实了其构象稳定性。傅里叶变换红外光谱法评估了制剂中胰岛素的稳定性。在等温条件下评估制剂的流变性能，所有制剂均表现出扩张行为。在优化的制剂和小鼠中的纯胰岛素进行体内研究，并监测 15 天的血糖水平。计算所有动物的血糖水平平均降低百分比，并使用方差分析进行分析。研究结果表明，与常规的每日一次胰岛素给药相比，这两种优化的制剂在控制血糖水平方面具有更好的药效学反应。进一步对皮下组织进行扫描电子显微镜研究和组织病理学检查，确定了制剂的生物相容性。
