羧甲基壳聚糖-聚乙二醇作为胰岛素载体的研究  

Preparation and characterization of PEG coupled carboxymethyl chitosan carrier for insulin

作　　者：吴珊珊[1] 熊富良[1] 宋豪源 李良红[1] 张雪琼[1] 

机构地区：[1]武汉理工大学化学化工与生命科学学院,湖北武汉430070

出　　处：《中国医院药学杂志》2017年第10期906-910,915,共6页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金项目(编号:51273156)

摘　　要：目的:制备胰岛素-羧甲基壳聚糖-聚乙二醇纳米粒。方法:利用红外光谱(FTIR)和核磁共振氢谱(~1 H-NMR)对羧甲基壳聚糖-聚乙二醇的结构进行表征,用粒度分析仪测定纳米粒的粒径分布及电位,采用动态透析法考察纳米粒的释药性能,用CCK-8试剂盒检测纳米粒细胞毒性,以糖尿病小鼠为模型,研究纳米粒的降血糖作用。结果:聚乙二醇成功接枝到羧甲基壳聚糖上,包埋胰岛素的纳米粒的平均粒径为(257.5±12.1)nm,Zeta电位为(-15.2±0.3)mV,负载胰岛素的羧甲基壳聚糖-聚乙二醇纳米粒在中性释放介质中,5 h内胰岛素的释放速度较快,之后8 h趋于平稳,胰岛素的累计释放量可达到80%,CCK-8试剂盒显示纳米粒对L929细胞基本无细胞毒性,50 U·kg^(-1)的纳米粒溶液经灌胃给药后,血糖浓度明显降低。结论:胰岛素-羧甲基壳聚糖-聚乙二醇纳米粒基本无毒性,具有良好的生物相容性,对糖尿病小鼠有效发挥降血糖作用。OBJECTIVE To prepare insulin loaded polyethylene glycol-carboxymethyl chitosan nanoparticles （CMC＆mPEG/ insulin NPs）. METItODR The structure of CMCS-mPEG was confirmed by FTIR and 1 H-NMR spectroscopy. The size distribution and zeta potential of CMCS-mPEG/insulin NPs were evaluated by laser particle size determination, drug-loading rate was determined by dynamic dialysis method, the eytotoxicity of nanoparticles was detected by CCK-8 kit, hypoglycemic activity was evaluated by montoring the blood sugar level of alloxan-induced diabetic mice. RESULTS PEG was successfully grafted to carboxymethyi chitosan. The average diameter of the nanoparticles was （257.5 ± 12. 1） nm, the mean electric potential was （ - 15.2± 0. 3） inV. Insulin realease in vitro exhibitted a rapid release in neutral medium in the frist five hours, and then became slow in the next eight hours, and the cumulative release rate of insulin was up to 80%. CCK-8 assay demonstrated that nanoparticles showed almost no toxicity to L929 cells. The blood glucose concentration was significantly decreased after intragastric administration of nanoparticles. CONCLUSION CMCS-mPEG/insulin nanoparticles with good biocompatibility and very low toxicity show effective hypoglycemic activity after oral administration in diabetic mice.

关 键 词：胰岛素 羧甲基壳聚糖 纳米粒 降血糖 

分 类 号：R94[医药卫生—药剂学]