口服载司美格鲁肽纳米球的制备及药效学评价  

Preparation and Pharmacodynamic Evaluation of Oral Delivery of Semaglutide Nanospheres

作　　者：隋东霖 韦祎[2] 朱裕 陈小强 马光辉[2] SUI Donglin;WEI Yi;ZHU Yu;CHEN Xiaoqiang;MA Guanghui(College of Chemical Engineering,Nanjing Tech University,Nanjing 211816,China;State Key Laboratory of Biochemical Engineering,Institute of Process Engineering,Chinese Academy of Sciences,Beijing 100190,China)

机构地区：[1]南京工业大学化工学院,南京211816 [2]中国科学院过程工程研究所生化工程国家重点实验室,北京100190

出　　处：《中国药学杂志》2024年第17期1629-1636,共8页Chinese Pharmaceutical Journal

基　　金：国家重点研发计划项目子课题项目资助(2023YFC2812001)。

摘　　要：目的制备用于口服递送司美格鲁肽的牛黄胆酸修饰的聚乳酸-羟基乙酸共聚物(PLGA)纳米球。方法以复乳溶剂挥发法制备载司美格鲁肽纳米球,通过单因素实验优化纳米球制备工艺;通过扫描电镜、傅里叶变换红外光谱和激光粒度仪对纳米球进行表征;使用SD大鼠进行药动学实验;使用db/db小鼠进行药效学实验。结果最优工艺制备出的纳米球粒径为(185.9±3.31)nm;ζ电位为(-32.53±0.95)mV;红外光谱表明,牛黄胆酸成功地修饰了纳米球表面;载药量和包埋率分别为(11.15±0.07)%和(85.51±0.01)%。纳米球在体外具有良好缓释效果,192 h内累计释放率达84.96%。在SD大鼠体内进行了药动学实验,实验结果表明,纳米球的生物利用度为2.5%,可在192 h内缓释司美格鲁肽。在db/db小鼠体内验证了纳米球的药效,结果显示,灌胃给药纳米球后,糖尿病小鼠血糖快速下降并保持稳定约3 d。结论本实验制备的口服载司美格鲁肽纳米球具有较高的载药量和包埋率,可以在3 d内有效控制糖尿病小鼠的血糖,提高生物利用度。OBJECTIVE To preparet aurocholic acid modified PLGA nanospheres for oral delivery of semaglutide.METHODS The nanospheres were prepared by dobule emulsion solvent evaporation technique,and the preparation process was optimized by single-factor experiments;the nanospheres were characterized by scanning electron microscopy,Fourier transform infrared spectroscopy and laser particle size measurement;pharmacokinetic experiments were performed using SD rats;pharmacodynamic experiments were performed using db/db mice.RESULTS The FT-IR showed that taurocholic acid was successfully modified to the surface of the nanospheres.The particle size of the nanospheres was(185.9±3.31)nm,theζ-potential was(-32.53±0.95)mV,and the drug loading and encapsulation rates were(11.15±0.07)%and(85.51±0.01)%.The nanospheres showed good sustained release in vitro,with a cumulative release rate of 84.96%within 192 h.Pharmacokinetic experiments were performed in SD rats,and the results showed that the bioavailability of nanospheres was 2.5%,and the slow release of semaglutide could be achieved within 192 h.The efficacy of nanospheres was verified in db/db mice,and the results showed that after gavage administration of nanospheres,the blood glucose of diabetic mice decreased rapidly and remained stable for about 3 d.CONCLUSION The oral delivery of semaglutide nanospheres prepared in this study has high drug loading and encapsulation efficiency,which can effectively control the blood glucose of diabetic mice within 3 d and improve the bioavailability.

关 键 词：纳米粒子 聚合物 肽 司美格鲁肽 口服递送 牛黄胆酸 

分 类 号：R944[医药卫生—药剂学]