2种自乳化递送系统的制备及其对斑马鱼炎症损伤部位“引药”作用  

Preparation of two self-emulsifying delivery systems and its medicinal usher effect on zebrafish with inflammatory injury

作　　者：刘欢欢 吴采栋 李琪琪 吴兴杰 陈英 沈祥春 魏茂陈 陶玲 LIU Huan-huan;WU Cai-dong;LI Qi-qi;WU Xing-jie;CHEN Ying;SHEN Xiang-chun;WEI Mao-chen;TAO Ling(Guizhou Engineer Center for Efficient Utilization of Natural Drugs,Key Laboratory of Pharmacology and Druggability Evaluation of Natural Drugs in Colleges and Universities of Guizhou Province,Key Laboratory of Excellent Utilization of Natural Drug Resources of Guizhou Medical University,School of Pharmacy,Guizhou Medical University,Guiyang 550025,China;Guiyang Xintian Pharmaceutical Co.,Ltd.,Guiyang 550025,China)

机构地区：[1]贵州省特色天然药物高效利用工程中心,贵州省高等学校天然药物药理与成药性评价特色重点实验室,贵州医科大学天然药物资源优效利用重点实验室,贵州医科大学药学院,贵州贵阳550025 [2]贵阳新天药业股份有限公司,贵州贵阳550025

出　　处：《中草药》2023年第16期5204-5213,共10页Chinese Traditional and Herbal Drugs

基　　金：贵州省科技计划项目(黔科合基础-ZK[2022]一般380);贵州省科技计划项目(黔科合基础-ZK[2023]一般303);贵州省高层次创新型人才百层次人才项目(贵州省科技庁黔科合人才[2015]No.4029);贵州医科大学药学国际科技合作基地(黔科合平台人才[2017]5802)。

摘　　要：目的以橄榄油和芝麻油分别作为油相进行自乳化递送系统(self-emulsifying drug delivery system,SEDDS)载体构建,考察2种SEDDS载体的药剂学性能及对斑马鱼体内炎症损伤部位递送差异。初步阐明辅料的“引药”效应,拟为炎症损伤部位有效递送材料的选择和辅料“引药达所”提供实验参考。方法结合相转变法和伪三元相图法筛选乳化剂、助乳化剂、乳化剂与助乳化剂质量比(K_(m)),星点设计-效应面法(central composite design-response surface methodology,CCDRSM)优化2种SEDDS载体处方;通过布鲁克海文纳米粒径仪测定2种SEDDS载体的中位径(D_(50))和ζ电位;利用立体荧光显微镜观察2种SEDDS载体在斑马鱼体内炎症损伤部位的递送差异。结果2种SEDDS最佳乳化剂和助乳化剂均为聚山梨酯80-无水乙醇(2∶1),最佳处方油相与K_(m)值均为1∶1,滴加适量纯水后呈半透明略带蓝色乳光液体;橄榄油和芝麻油SEDDS最佳处方D_(50)分别为(219.36±14.86)、(225.06±13.66)nm,ζ电位分别为(-3.13±0.55)、(3.58±0.10)m V。与正常组比较,2种SEDDS在炎症损伤斑马鱼体内的总荧光强度具有极显著性差异(P<0.001),相比于橄榄油SEDDS,芝麻油SEDDS在炎症损伤部位富集效果更为突出,二者主要分布在心脏和肝脏部位。结论2种SEDDS载体制备方法简单,外观良好。阐明油相因素带来的递送差异,可以为不同炎症损伤部位的有效递送材料选择、为辅料发挥“引药”作用提供实验参考。Objective To construct the self-emulsifying drug delivery system(SEDDS)carriers using olive oil and sesame oil as the oil phase to investigate the pharmacologic properties and delivery differences of two SEDDS carriers to the inflammation injured sitesin zebrafish.The medicinal usher effect of excipients was preliminaries elucidated,so as to provide experimental reference for the selection of effective delivery materials for the site of inflammatory injury and the medicinal usher effect of excipients.Methods The emulsifier,coemulsifier and Km value were screened by phase transition method and pseudo-ternary phase diagram method.The carrier prescription of SEDDS was optimized by central composite design-response surface method.The partical size(D_(50))and ζ potential of two SEDDS carriers were determined by Brookhaven nanosize analyzer.Three-dimensional fluorescence microscopy was used to observe its delivery difference in inflammatory injury site of zebrafish.Results The emulsifying effect was the best when the oil phase and Km value of the two SEDDS were 1:1.The best emulsifier and coemulsifier was Tween 80-anhydrous ethanol(2:1),which was translucent and bluish milky liquid after adding proper amount of pure water.The optimal D_(50) of self-emulsifying carriers of olive oil and the sesame oil were(219.36±14.86)nm and(225.06±13.66)nm,respectively.The ζ potentials were(−3.13±0.55)mV and(3.58±0.10)mV,respectively.The total fluorescence intensity of the two SEDDS carriers in the inflammatory zebrafish was stronger than that in the normal group(P<0.001).Compared with the olive oil self-emulsifying,the enrichment effect of the sesame oil SEDDS was more prominent in the injured site of inflammation.They were mainly distributed in the heart and liver.Conclusion The preparation methods of the two SEDDS carriers were simple and good in appearance.The difference in delivery caused by oil phase factors can provide material selection for effective delivery to different inflammatory injury sites,which provide experim

关 键 词：引药 炎症损伤 斑马鱼 自乳化递送系统 递送效应 橄榄油 芝麻油 油相 药剂学性能 相转变法 伪三元相图法 星点设计-效应面法 

分 类 号：R283.6[医药卫生—中药学]