胡桃醌F127/TPGS混合胶束的制备及其对溃疡性结肠炎的治疗作用  

Preparation of mixed micelles of juglone F127/TPGS and their therapeutic effects on ulcerative colitis

作　　者：崔莉[1,2] 刘芮奇 孙娥[1,2] 钟荣玲[1,2] 魏兰福[1,2] CUI Li;LIU Ruiqi;SUN E;ZHONG Rongling;WEI Lanfu(The Third Clinical Medical College,Nanjing University of Chinese Medicine,Nanjing 210028,China;Jiangsu Province Academy of Traditional Chinese Medicine,Nanjing 210028,China)

机构地区：[1]南京中医药大学第三临床医学院,南京210028 [2]江苏省中医药研究院,南京210028

出　　处：《西北药学杂志》2024年第3期70-76,共7页Northwest Pharmaceutical Journal

基　　金：国家自然科学基金项目(编号:81403121);江苏省中医药科技发展计划项目(编号:MS2021025);南京中医药大学自然科学基金项目(编号:XZR2020025)。

摘　　要：目的优化胡桃醌普郎尼克F127(F127)/聚乙二醇琥珀酸酯(D-alpha tocopheryl polythylene glycol succinate,TPGS)混合胶束的制备工艺,并对该混合胶束进行表征和体内药效学研究。方法用薄膜分散法制备胡桃醌F127/TPGS混合胶束,以包封率为指标,用单因素和3因素3水平响应面实验优化胡桃醌混合胶束的制备工艺。用透射电镜和马尔文粒度仪对混合胶束进行表征。用透析袋研究其体外释放度。通过疾病活动指数(DAI)和结肠HE切片研究胡桃醌F127/TPGS混合胶束体内抗溃疡性结肠炎作用。结果胡桃醌F127/TPGS混合胶束的最佳制备工艺:药物∶载体=1∶50、F127∶FPGS=4∶5、水化体积为10 mL、水化时间为1 h、乙醇体积为1 mL。对最优处方进行验证,得到胡桃醌的平均包封率为90.53%,与预测值(85.32%)偏差较小。透射电镜下混合胶束呈球形,形态完整且分布均匀。平均电位为(−3.86±3.05)mV,平均粒径为(13.91±0.15)nm,PDI为(0.092±0.009)。体外释放度实验结果显示,胡桃醌F127/TPGS混合胶束的累积释放度大于胡桃醌混悬液。胡桃醌F127/TPGS混合胶束干预后,小鼠DAI值下降,结肠组织病理损伤得到缓解。结论经响应面优化的胡桃醌F127/TPGS混合胶束制备工艺条件稳定,且可增加胡桃醌溶解度,增强胡桃醌抗溃疡性结肠炎的作用。Objective To optimize the preparation process of mixed micelles of juglone F127/D-alpha tocopheryl polythylene glycol succinate(F127/TPGS),and to study the characterization and pharmacodynamics of the mixed micelles.Methods The mixed micelles of juglone F127/TPGS were prepared by thin film dispersion method.With the encapsulation rate as index,single-factor and three-factor and three-level response surface tests were used to optimize the preparation process of walnut quinone mixed micelles.The mixed micelles were characterized by transmission electron microscopy(TEM)and Malvern particle size analyzer.The release of the micelles in vitro was studied by dialysis bag.The anti-ulcerative colitis effect of juglone F127/TPGS mixed micelles in vivo was studied by disease activity index(DAI)and colon HE sections.Results The optimal preparation conditions were as follows:juglone/carrier=1∶50,F127∶FPGS=4∶5,the hydration volume 10 mL,the hydration time 1 hour,and the ethanol volume 1 mL.After verification,the average encapsulation rate of juglone was 90.53%,which had little deviation from the predicted value of 85.32%.The mixed micelles of juglone F127/TPGS were spherical in shape and uniform in distribution under TEM.The average potential was(−3.86±3.05)mV,the average particle size was(13.91±0.15)nm,and the PDI was(0.092±0.009).The results of release test showed that the cumulative release of F127/TPGS micelles was greater than that of juglone suspension.With the intervention of juglone F127/TPGS mixed micelles,DAI value of mice decreased,the pathological injury of colon tissue was relieved.Conclusion The optimized preparation of juglone F127/TPGS mixed micelles was stable and can increase the solubility of juglone and enhance the anti-ulcerative colitis effect of juglone.

关 键 词：胡桃醌 Box-Behnken响应面法 F127 聚乙二醇琥珀酸酯 混合胶束 

分 类 号：R965[医药卫生—药理学]