HA-GMS-INS胰岛素口服纳米给药系统研究

Oral nano drug delivery system of HA-GMS-INS insulin

目的:建立透明质酸-单硬脂酸甘油酯-胰岛素(HA-GMS-INS)口服纳米给药系统,并进行成药性研究。方法:利用酯化反应合成载体HA-GMS,单因素法筛选制备工艺,通过红外光谱和核磁共振氢谱对结构进行表征;采用低能乳化法制备HA-GMS-INS,用多分散激光粒度仪和透射电镜测定纳米乳的粒径及形态,并对胰岛素的体外释放性能、抗酶解作用进行考察。以糖尿病小鼠为模型进一步考察HA-GMS-INS口服降血糖作用。结果:优化制得的纳米乳外观形态圆整,平均粒径为37.19 nm。在模拟人工胃液的释放介质中,累积释放度2 h时达到40%左右,在模拟人工肠液的释放介质中,6 h释放完全。对胃蛋白酶和胰蛋白酶的抗酶解作用实验结果表明,以HA-GMS为载体的载胰岛素口服纳米乳对胰岛素有一定的保护作用;HA-GMS载胰岛素纳米乳与其他三组比较,降糖效果显著,在给药后的6 h时血糖值降为初始血糖值的72.3%。结论:HA-GMS-INS口服纳米给药系统,能增加INS在胃肠道内的稳定性,提高对糖尿病小鼠的降血糖作用。

OBJECTIVE To establish an oral nano-drug delivery system of hyaluronic acid-glycerymonostearate-insulin(HA-GMS-INS). METHODS After preparation by low-energy emulsification,HA-GMS-INS was screened by single-factor method and its structure characterized by infrared spectroscopy and nuclear magnetic resonance hydrogen spectroscopy.Particle size and morphology of nanoemulsion were determined by laser analyzer and transmission electron microscope.And in vitro release performance and anti-enzymatic hydrolysis were also examined.A diabetic mice model was utilized for elucidating its oral hypoglycemic effect. RESULTS The optimized nanoemulsion has a round appearance with an average particle size of 37.19 nm.In release medium of simulated gastric fluid,the cumulative release degree reached around 40%at 2 h;in release medium of simulated intestinal fluid,release completed at 6 h.The experimental results of anti-enzymolysis for pepsin and trypsin demonstrated that insulin-loaded oral nanoemulsion with HA-GMS as a carrier had a certain protective effect on insulin.Compared with another three groups,HA-GMS insulin nanoemulsion had marked hypoglycemic effect and blood glucose level dropped to 72.3%of initial blood glucose level at 6 h after dosing. CONCLUSION Oral nano drug delivery system of HA-GMS-INS may boost the stability of INS in gastrointestinal tract and improve the hypoglycemic effect in diabetic mice.