胰岛素纳米粒子缓释制剂的实验研究

Experimental Study on the Effect of Nanoparticle Slow Releasing Preparation of Insulin

目的 研究胰岛素纳米级粒子缓释制剂的体内生物作用 ,以期在临床上实现胰岛素注射剂的更长效稳定释放给药治疗糖尿病。方法 以聚乳酸 -聚乙醇酸共聚物 (PLGA)作为基质材料 ,采用超声乳化 /溶剂挥发法制备PLGA包囊胰岛素的纳米级微粒 (NP) ,借助扫描电镜观察微粒形态 ,通过激光光散射实验测定纳米微粒的粒径分布 ;利用高效液相色谱 (HPLC)测定纳米微粒制剂的载药率 ;并做纳米胰岛素制剂在糖尿病动物模型体内的药效学研究。结果经电镜观察PLGA -胰岛素NP为表面光滑的球形微粒 ,粒径分布平均值是 112 4nm ,呈正态分布 ;PLGA -胰岛素NP载药率为 7 4 % ;体内研究表明 ,所制备的纳米制剂生物活性没有改变 ;皮下注射途径给药纳米胰岛素可以在至少 72小时内长效控释 ,有效降低血糖并保持在正常范围。此外纳米制剂的量 -效关系明显 ,未见任何不良反应。结论PLGA纳米粒子可以作为胰岛素的有效载体 ,达到更长效稳定控制释放的目的 ,发挥药物更佳的降糖作用。

Objective The preparation technique and blood glucose regulating effect of a nanoparticle slow released preparation of insulin were studied in vivo.Methods The polylactate-polyethanol acid copolymer(PLGA) microencapsulated insulin of nanoparticles(NP) was prepared by using PLGA as matrix and ultrasound emulsification/dissolvent volatilization. The morphology of the nanoparticle was observed with scanning electron microscope and its diameter was determined by laser emission. The drug carrying ratio of this preparation was determined by high performance liquid chromatograph(HPLC), and its pharmacodynamics in diabetic animal model was studied. Results It showed that the characteristics of PLGA insulin NP was as follow:①smooth surface;②112.4μm in average diameter, with normal distribution;③drug carrying ratio 7.4%. It was demonstrated in vivo that there was no difference in biological activity from that in vitro. It showed that it provided slow releasing within at least 72h effectively in lowering blood glucose and keeping it in normal range. There was apparent dosage-effective relationship. Any of adverse effects was not occurred.Conclusion Nanoparticles may be adopted as an effective carrier of insulin achieving of long performing and stable releasing of insulin and resulted in more effective in lowering blood glucose.