肠溶包衣胰岛素-壳聚糖复合物纳米粒的制备及体内外性质

目的制备肠溶包衣的胰岛素壳聚糖复合物纳米粒,并对其理化性质、体外释药以及在糖尿病模型大鼠体内的降血糖效果进行研究。方法采用离子交联法制备胰岛素壳聚糖复合物纳米粒,使用羟丙基甲基纤维素酞酸酯(HP55)对其进行肠溶包衣;通过扫描电子显微镜观察其表观形态,用激光粒度测定仪测定其粒径大小,用Zeta电势测定仪测定其Zeta电势,使用HPLC法测定离心上清夜中胰岛素浓度,计算包封率。结果制备得到的纳米粒均匀、圆整,包衣前后粒径分别为(281±10)nm和(328±13)nm,Zeta电势分别为(30.4±6.97)mV和(33.7±6.69)mV,包封率分别为78.5%和74.3%;肠溶包衣纳米粒在人工胃液和肠液中的释药速率均明显低于未包衣纳米粒,突释效应显著减小;未包衣复合物纳米粒能够显著降低糖尿病模型大鼠的血糖浓度,其降糖效果能持续20 h以上,肠溶包衣后,降糖效果明显增强;肠溶包衣前后在模型大鼠体内24 h相对生物利用度分别为11.12%和16.29%。结论肠溶包衣胰岛素壳聚糖复合物纳米粒可以有效抑制胰岛素的突释,促进其吸收,显著降低模型大鼠的血糖浓度,能够作为胰岛素口服给药的有效载体。

Study of enteric-coated insulin-chitosan complex nanoparticles

Objective To prepare enteric-coated insulin-chitosan complex nanoparticles(EICCN),and characterize the physicochemical properties,in vitro release behavior and hypoglycemic effects in diabetic rats.Methods ICCN were formulated through ionic cross linking method,and then enteric-coated by HP55.Their particle size and zeta potential were measured by Coulter Delsa 440 SX and Coulter LS Series,respectively.The entrapment efficiency of insulin was calculated through determining the concentration of insulin in the supernatant after centrifugation.The release behavior in PBS with pH value of 1.2 and 7.4 were studied.The hypoglycemic effects in diabetic rats were investigated.Results The nanoparticles were homogenous and well global.The particle size and zeta potential of nanoparticles with or without enteric coating were((281±)10) nm and(328±13) nm,(30.4±6.97) mV and(33.7±6.69) mV,respectively.The entrapment efficiency of insulin were 78.5% and 74.3%,respectively.The formation of complex between insulin and chitosan reduced the burst release magnificently and the release rate of insulin in EICCN was much more slowly than that in ICCN.Both ICCN and EICCN could effectively decrease the serum glucose levels in diabetic rats and the hypoglycemic effects could maintain for more than 20 h.The enteric coating could increase the hypoglycemic effect of the nanoparticles significantly.And the relative bioavailability of ICCN and EICCN were 11.12% and 16.29%,respectively.Conclusions Because the EICCN could increase the entrapment of insulin,inhibit the burst release of insulin and enhance the hypoglycemic effect in diabetic rats,they could be useful carrier for the oral administration of insulin.