胰岛素巯基化透明质酸纳米粒的制备与体外性质评价

Preparation and evaluation of insulin thiolated hyaluronic acid nanoparticles in vitro

目的制备胰岛素巯基化透明质酸纳米粒(insulin thiolated hyaluronic acid nanoparticles,Ins-HA-Cys-NPs),考察纳米粒的理化性质。方法以合成的具有生物黏附性质的巯基化透明质酸作为载体,采用超声乳化法制备纳米粒,考察其外观、粒径、Zeta电位、包封率、载药量,并进行其冻干制剂的冻干保护剂筛选。结果制备的Ins-HA-Cys-NPs粒径均一,外观圆整;平均粒径为(178.5±0.8)nm,PDI为(0.214±0.013),Zeta电位为-(38.47±0.46)mV,超滤离心法测定载药纳米粒的包封率为(48.85±0.66)%,载药量为(4.79±0.13)%;选择10%的甘露醇为冻干保护剂,复溶后得到具有蓝色乳光的粒径均一的纳米粒混悬液。结论巯基化透明质酸纳米粒是蛋白多肽类药物口服给药的潜在载体,为下一步研究胰岛素纳米粒在大鼠体内药效、药动学研究提供前提和基础。

Objective To prepare insulin thiolated hyaluronic acid nanoparticles( Ins-HA-Cys-NPs) and study its physicochemical properties.Methods The Ins-HA-Cys-NPs was prepared by ultrasonic emulsifying method,and the properties of nanoparticles including morphology,mean diameter,Zeta potential,entrapment efficiency and drug loading efficiency were studied,as well as the cryoprotectant selection. Results The prepared nanoparticles was round in appearance and the mean diameter was( 178. 5 ± 0. 8) nm,the polydispersity index was( 0. 214 ± 0. 013) and the Zeta potential was-( 38. 47 ± 0. 46) mV,while the entrapment efficiency was( 48. 85 ± 0. 66) %,drug loading efficiency was( 4. 79 ± 0. 13) %; 10%mannitol as cryoprotectant provided uniform and well dispersed suspension of nanoparticles with blue opalescence after redispersion. Conclusion The thiolated hyaluronic acid nanoparticles may be used as the carrier for oral drug delivery system of insulin,and it provides a basis for studies on rats in vivo.