葡萄糖敏感型二氧化硅载胰岛素体系的制备与初步评价

Preparation and evaluation of a glucose-sensitive silica loaded insulin drug delivery system

目的制备葡萄糖敏感型二氧化硅载胰岛素体系,对其葡萄糖响应性释放胰岛素及降血糖效果进行初步评价。方法采用有机模板法制备介孔二氧化硅载体,以透射电镜、比表面积与孔径分析仪、动态光散射仪对该载体进行表征;以胰岛素为模型药物,采用吸附平衡法载药;以3-羧基苯硼酸接枝壳聚糖制备葡萄糖敏感材料,通过氢键作用将葡萄糖敏感材料包覆于载药二氧化硅表面制得葡萄糖敏感载药体系;以HNMR、IR、TG等对葡萄糖敏感材料的结构及包覆量进行考察。采用高效液相色谱法对载药体系的载药量及药物的累计释放度进行测定;建立糖尿病小鼠模型,考察载药体系的体内降血糖效果。结果制备的介孔二氧化硅载体孔径为13 nm,对胰岛素载药量为27. 4%;经计算葡萄糖敏感材料的包覆量为10. 7%;释放介质中无葡萄糖时,载药体系基本不释药、葡萄糖质量浓度为10 g·L-1时,1 h内累计释药量增至42. 7%;制得的葡萄糖敏感型胰岛素二氧化硅载药体系按30 IU·kg-1胰岛素计量给药,6 h血糖降低22. 7%。结论设计制备的葡萄糖敏感型二氧化硅载胰岛素体系具有葡萄糖响应性释药功能及一定的体内降血糖效果。

Objective To prepare a glucose-sensitive INS/MCF drug delivery system and evaluate its glucose-responsive drug release and hypoglycemic effect.Methods Organic template method was used to prepare the silica.Transmission electron microscopy,nitrogen adsorption-desorption and dynamic light scattering were adopted to characterize the silica.Insulin as a model drug,was loaded by adsorption equilibrium method.Glucose-sensitive material was synthesized using 3-carboxyphenylboronic acid and chitosan,and coated on the surface of the silica to prepare a glucose-sensitive drug delivery system.The structure and coating amount of the glucose-sensitive material were investigated by HNMR,IR and TG.The drug loading and the cumulative drug release were measured by high performance liquid chromatography.A diabetic mouse model was established to examine the hypoglycemic effect of the drug delivery system in vivo.Results The pore size of the mesoporous silica carrier was 13 nm,drug load was measured to be27.4%,the coating amount was 10.7%.When glucose was not added,insulin did not release from the carrier,and when the glucose concentration was 10 g·L-1,the cumulative drug release significantly increased by 42.7%.In vivo pharmacodynamic experiments showed the glucose-sensitive INS/MCF drug delivery system had a certain hypoglycemic effect,and at 6 hours blood glucose dropped 22.7%.Conclusion The INS/MCF drug delivery system coated with glucose-sensitive material has obvious glucose-responsive drug release function and a certain hypoglycemic effect.