胰岛素海藻酸钠纳米粒的制备及体内外评价

Preparation of Insulin-loaded Sodium Alginate Nanoparticles and Its Pharmacodynamics Study on Diabetic Rats

目的制备具有较高药物包封率的胰岛素海藻酸钠纳米粒(insulin-loaded sodium alginate nanoparticles,INS-SA-NP),考察其对糖尿病模型大鼠的降血糖作用。方法以胰岛素为模型药物,采用溶剂扩散法制备胰岛素海藻酸钠纳米粒,考察制备工艺对纳米粒粒径和电位的影响,测定药物包封率。采用糖尿病模型大鼠经呼吸道插入给药,评价胰岛素海藻酸钠纳米粒的降血糖作用。结果胰岛素海藻酸钠纳米粒的平均粒径416.4 nm,Zeta电位值(-92.6±1.8)mV,平均包封率(89.72±3.90)%;该纳米粒经呼吸道插入给药后,以皮下注射胰岛素溶液1 u.kg-1为对照,其相对生物利用度达到61.64%,维持降血糖作用的时间明显延长。结论以溶剂扩散法制备得到的胰岛素海藻酸钠纳米粒,具有较高的药物包封率,该纳米粒经大鼠呼吸道插入给药后,降血糖作用显著延长。

OBJECTIVE To prepare insulin-loaded sodium alginate nanoparticles with high entrapment efficacy and investigate the hypoglycemic effects in diabetic rats. METHODS Insulin-loaded sodium alginate nanoparticles was prepared by solvent diffusion method. Insulin was incorporated to investigate the effect of drug incorporation on nanoparticles size, Zeta potential （charge） and entrapment efficacy. The diabetic rats model was established and evaluate the hypoglycemic effects following pulmonary delivery of insulin-loaded sodium alginate nanoparticles. RESULTS The diameter of insulin-loaded sodium alginate nanoparticles was 416.4 nm and the mean entrapment was （89.72 ±3.90） %. The bioavailability of insulin-loaded sodium alginate nanoparticles delivered through pulmonary was 61.64% compared to subcutaneons inject insulin solution 1 u·kg^-1, the hypoglycemic effect maintained longer. CONCLUSION Insulin-loaded sodium alginate nanoparticles prepared by solvent diffusion technique show a higher entrapment efficiency. When dehvered to diabetic rats, it can significantly reduced blood glucose level by subcutaneous as well as pulmonary delivery maintained effect for longer time.