温敏接枝共聚物瓜耳胶-g-异丙基丙烯酰胺水凝胶胰岛素埋植剂

Investigation on the implantable thermo-sensitive hydrogels constructed with graft copolymers of poly(N-isopropylacrylamide)-g-guar gum and insulin

目的将温敏接枝共聚物瓜耳胶-g-异丙基丙烯酰胺(GPNA)制成含胰岛素的凝胶埋植剂,考察埋植凝胶剂生物相容性及其中胰岛素的药效学特征。方法短期相容性试验考察GPNA凝胶的生物相容性;对糖尿病大鼠分别皮下埋植胰岛素凝胶1.25×10-3g.kg-1和皮下注射4.167×10-5g.kg-1胰岛素注射液,不同时间、不同温度条件下考察凝胶中胰岛素释放情况。结果GPNA凝胶剂有很好的生物相容性;实验动物组内各时间点血糖浓度间不存在明显差别,组间各时间点血糖浓度间存在着显著性差别;在温度降低时间点血糖浓度明显低,与皮下注射组进行t-检验,无显著性差异,在正常体温时,血糖浓度有升高迹象,与皮下注射组进行t-检验,有显著性差异;胰岛素凝胶的相对生物利用度为2.47%。结论温敏型胰岛素凝胶的体内释药具有明显的温度依赖性,可以通过控制外部温度调节凝胶内药物的释放速率。

Objective To inspect the safety, the biocompatibility of poly （N-isopropylacrylamide） -g-guar gum hydrogel, which is used as the cartier in planted drug delivery system. Methods The biocompatibility was studied by short-term biocompatibility test. The rat, whose blood glucose was more than 2.5 g·L^-1was chosen as the diabetes model. The insulin releases were examined in male rats, which was implanted with insulin（ 1. 250×10-3 g·kg^-1 ） hydrogel or subcutaneously injected insulin by 4. 167 ×10-5g·kg^-1 Results GPNA [ guar gum-g-poly（N-isopropylacrylamide） ] hydrogels had good biocompatibility. The blood glucose levels had obvious difference between the two groups and had no difference in the same group. The blood glucose of the rats reduced obviously with the decrease of temperature, while the blood glucose of the rats rose at normal temperature. The bioavailability calculated by the blood glucose level versus time profiles was 2. 47 %. Conclusions The GPNA [ guar gum-g-poly （N-isopropylacrylamide） ] hydrogel loaded insulin has obvious temperature sensitivity. The rate of drug release changes with the change of temperature.