摘要
目的优化1,8-桉叶油素(1,8-cineole,1,8-Cin)自微乳给药系统(1,8-cineole self-microemulsion drug delivery system,1,8-Cin-SMEDDS)处方,对其进行表征并进行细胞摄取考察。方法通过绘制伪三元相图,确定1,8-Cin-SMEDDS有效自乳化区域,进行初步处方筛选。以粒径和载药量为指标,采用星点设计-效应面法对1,8-Cin-SMEDDS处方进行优化并验证。荧光显微镜观察高糖损伤的人脐静脉内皮细胞(HUVEC)对1,8-Cin-SMEDDS的摄取情况。结果1,8-Cin-SMEDDS的最佳处方是大豆油(7.5%)与1,8-Cin(22.5%)为混合油相,HS15(56%)为乳化剂,乙醇(14%)为助乳化剂,滴加纯水至8m L得半透明略带蓝色乳光液体。透射电镜观察其外观呈球形液滴,激光粒度Zeta电位测定仪测得平均粒径为(131.68±1.44)nm,Zeta电位为(-10.03±1.63)m V;HPLC法测得包封率为(99.890±0.012)%,载药量为(224.750±0.028)mg/g。HUVEC细胞摄取实验结果表明,细胞对1,8-Cin-SMEDDS的摄取高于游离1,8-Cin。结论1,8-Cin-SMEDDS制备方法简便,重复性好,所得1,8-Cin-SMEDDS外观良好,包封率高,理化性质稳定,且能促进细胞摄取。
Objective To optimize the formulation of 1,8-cineole self-microemulsifying drug delivery system(1,8-Cin-SMEDDS),characterize it and investigate its cell uptake.Methods By drawing pseudo-ternary phase diagram,the effective self-emulsifying region of 1,8-Cin-SMEDDS was determined,and the preliminary prescription was screened.Taking the particle size and drug loading as the index,the central composite design-response surface method was used to optimize and verify the prescription.Fluorescence microscope was used to observe the uptake of human umbilical vein endothelial cells(HUVEC)injured by high glucose.Results The results showed that the best prescription of 1,8-Cin-SMEDDS was a mixture of soybean oil(7.5%)and 1,8-Cin(22.5%),HS15(56%)as emulsifier,ethanol(14%)as co-emulsifier,and dripping pure water to 8 m L to obtain a translucent slightly bluish emulsion.The appearance of spherical droplets was observed by transmission electron microscope,and the average particle size and Zeta potential measured by laser particle size Zeta tester was(131.68±1.44)nm and(-10.03±1.63)m V,respectively;The entrapment efficiency estimated by HPLC was(99.890±0.012)%,and the drug loading was(224.750±0.028)mg/g.The results of HUVEC cell uptake assay showed that the uptake of 1,8-Cin-SMEDDS by cells was higher than that of free 1,8-Cin.Conclusion The preparation method of 1,8-Cin-SMEDDS is simple and reproducible.The obtained method has good appearance,high entrapment efficiency,stable physical,and chemical properties,which can also promote cell uptake.
作者
李婉蓉
王菲
陈建波
杨佳佳
杨增秋
杨贵前
宋朔尧
肖婷
周雪
吴林菁
张敏
沈祥春
陶玲
LI Wan-rong;WANG Fei;CHEN Jian-bo;YANG Jia-jia;YANG Zeng-qiu;YANG Gui-qian;SONG Suoyao;XIAO Ting;ZHOU Xue;WU Ling-jing;ZHANG Min;SHEN Xiang-chun;TAO Ling(Guizhou Provincial Center for Efficient Utilization of Natural Drugs,Key Laboratory of Pharmacology and Drug 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;School of Basic Medical Sciences,Guizhou Medical University,Guiyang 550025,China)
出处
《中草药》
CAS
CSCD
北大核心
2020年第9期2418-2426,共9页
Chinese Traditional and Herbal Drugs
基金
贵州省科技计划项目(黔科合支撑[2017]2891)
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)
贵州省高层次创新型人才百层次人才项目(贵州科技厅黔科合人才[2015]4029号)
贵州省科技创新人才团队项目(黔科合人才团队[2015]4025号)
贵州省教育厅拔尖人才计划项目(黔教合KY2016[073])。
关键词
1
8-桉叶油素
自微乳
伪三元相图
星点设计-效应面法
细胞摄取
人脐静脉内皮细胞
1,8-cineole
self-microemulsion
pseudo ternary phase diagram
central composite design-response surface method
cell uptake
human umbilical vein endothelial cells
作者简介
李婉蓉,在读硕士,从事中药民族药新药研发和药物新剂型及新技术研究。Tel:15761602593 E-mail:1292312348@qq.com;通信作者:沈祥春,博士,教授,从事心血管药物药理、功能天然产物化学及生物学研究。Tel:(0851)88416149,E-mail:shenxiangchun@126.com;通信作者:陶玲,硕士,教授,从事中药民族药和药物新剂型及新技术研究。Tel:(0851)8416160,E-mail:649511230@qq.com。
