黏膜特异性多肽修饰载胰岛素口服纳米粒的制备及其体内外评价

CSK-conjugated PLGA nanoparticles enhance oral delivery of insulin

目的构建黏膜细胞特异性多肽(CSK)修饰的载胰岛素(insulin,INS)口服纳米粒(CSK—INS—NPs),并对其体外性质以及体内降血糖效果进行评价。方法用复乳法制备CSK修饰的载胰岛素聚乳酸羟基乙酸(poly lactic—co—glycolic acid,PLGA)纳米粒,对其理化性质和包封率进行考察。通过体外人克隆结肠腺癌细胞(Caco—2)摄取实验考察CSK修饰的纳米粒的细胞穿透能力和跨膜能力。构建糖尿病模型大鼠评价口服纳米粒的降血糖能力。结果制备得到的CSK—INS—NPs粒径为(134.4±15)nm,粒径多分散系数小于0.3,胰岛素的包封率(EE%)为71%。体外Caco—2细胞摄取实验表明,细胞对CSK—INS—NPs摄取量是INS—NPs的2.8倍。相比于INS—NPs,CSK—INS—NPs能够更加高效的穿透Caco—2细胞层。糖尿病大鼠的降糖实验表明,在10 h内,口服CSK—INS—NPs能够降低血糖浓度,且保持稳定。结论 CSK能够促进载胰岛素纳米粒跨越Caco—2细胞膜,CSK—INS—NPs是一种潜在的高效口服胰岛素载体给药系统。

Objective To investigate the effects of CSK-conjugated PLGA nanoparticles on oral delivery of insulin in vitro and in vivo.Method CSK-INS-NPs were prepared by double-emulsion. Nanoparticle size、zeta potential and entrapment efficiency were measured. The efficiency of cellular uptake on Caco-2 cells in vitro was evaluated. The hypoglycemic effects were evaluated by monitoring the glucose levels in diabetic rats. Results The average sizes was(134. 4 ± 15)nm and their PDI values were less than 0.3.The insulin entrapment efifciency was around 71%. The cellular uptake of CSK-INS-NPs by Caco-2 cells was 2.8 times higher than INS-NPs. The CSK-INS-NPs transferred more insulin across the Caco-2 cell monolayer than INS-NPs and insulin solution did. In vivo experiments,the CSK-INS-NPs could reduce the blood glucose level of diabetic rats after oral administration in 10 h.Conclusion Compared with insulin solution,CSK-INS-NPs enhanced the insulin through Caco-2 cell monolayer by transcellular pathway and may be a potential delivery system for Oral Delivery of Insulin.