白蛋白-奥曲肽纳米颗粒制备及其缓释性能

Preparation and its sustained-release properties of albumin-octreotide nanoparticles

采用反溶剂法制备白蛋白纳米颗粒;通过单因素实验和Z分综合评价法对比不同交联剂的作用效果;研究白蛋白质量浓度、醇水体积比、脱溶温度、溶剂pH、交联时间等工艺参数对白蛋白纳米颗粒性能的影响,确定优选工艺条件;运用浸渍吸附-冷冻干燥法构建白蛋白-奥曲肽微粉,考察微粉的载药量和体外溶出性能。结果表明:戊二醛为优选交联剂;当白蛋白质量浓度为10 g/L、醇水体积比为2∶1、脱溶温度为20℃、溶剂pH为9、交联时间为24 h时,制备白蛋白纳米颗粒的工艺条件最优,所制备白蛋白纳米颗粒的平均粒径为(100.6±2.5)nm,多分散指数为0.13±0.01,储存稳定性好;白蛋白-奥曲肽微粉能保持白蛋白载体原有的球状规则形貌,持续释药时间为2160 min,具有较好的体外释放性能。

Albumin nanoparticles were prepared by reverse solvent method.The effects of different crosslinking agents were compared by single factor experiment and Z-score comprehensive evaluation method.The effects of albumin mass concentration,the volumn ratio of alcohol to water,desolubilization temperature,solvent pH,crosslinking time and other process parameters on the performance of albumin nanoparticles were studied to determine the optimal process conditions.Albumin octreotide micropowder was prepared by impregnation adsorption-freeze-drying method.The drug loading capacity and in vitro dissolution performance of the micropowder were investigated.The results show that glutaraldehyde is the preferred crosslinking agent.When the albumin mass concentration is 10 g/L,the volume ratio of alcohol to water is 2∶1,the desolubilization temperature is 20℃,the solvent pH is 9,and the cross-linking time is 24 h,the preparation conditions of the albumin nanoparticles are the best.The average particle size of the prepared albumin nanoparticles is(100.6±2.5)nm,the polydispersion index is 0.13±0.01,and the storage stability was good.Albumin-octreotide micropowder maintains the original spherical morphology of albumin carrier,and the continuous release time is 2160 min,showing good in vitro release performance.