双氢青蒿素自微乳给药系统的制备及其评价  

Preparation and evaluation of dihydroartemisinin self-microemulsion drug delivery system

作　　者：张然 杨冰 廖茂梁[2,3,4] 华洁 周钰通[2,3,4] 周福军 张铁军 ZHANG Ran;YANG Bing;LIAO Mao-liang;HUA Jie;ZHOU Yu-tong;ZHOU Fu-jun;ZHANG Tie-jun(Tianjin Medical University,Tianjin 300070,China;Tianjin Institute of Phannaceutical Research,Tianjin 300462,China;Tianjin Key Laboratory of Quality Markers of Traditional Chinese Medicine,Tianjin 300462,China;State Key Laboratory of Drug Delivery and Pharmacokinetics,Tianjin 300462,China)

机构地区：[1]天津医科大学,天津300070 [2]天津药物研究院,天津300462 [3]天津市中药质量标志物重点实验室,天津300462 [4]释药技术与药代动力学国家重点实验室,天津300462

出　　处：《中草药》2021年第5期1291-1302,共12页Chinese Traditional and Herbal Drugs

基　　金：国家重大科技专项(2017ZX09101002-001-005)。

摘　　要：目的研究双氢青蒿素(dihydroartemisinin,DHA)自微乳给药系统(self-microemulsiondrugdeliverysystem,SMEDDS)(DHA-SMEDDS)的处方与制备工艺,并对其进行评价。方法通过溶解度实验、油相与乳化剂和助乳化剂配伍实验及伪三元相图的绘制,筛选DHA-SMEDDS的处方组成;以平均粒径、载药量为评价指标,采用星点设计-效应面法优化处方,并对DHA-SMEDDS的理化性质、初步稳定性进行评价。考察DHA-SMEDDS在马丁达比犬肾上皮MDCK细胞模型中促渗机制。结果优化后的DHA-SMEDDS处方中油相为辛癸酸甘油酯(15%)、乳化剂为聚氧乙烯40蓖麻油(46.4%)、混合助乳化剂为无水乙醇(24.12%)和聚乙二醇400(14.48%)。所得自微乳外观均一透明,自乳化后平均粒径(24.55±0.18)nm,多分散性指数(PDI)为0.092±0.028,电位为(-3.16±0.14)m V,载药量为(9.64±0.01)mg/g,包封率为(99.67±0.10)%,乳化时间为(13.90±0.10)s。初步稳定性实验表明,DHA-SMEDDS应常温避光保存。DHA-SMEDDS可以打开细胞间的紧密连接蛋白,降低细胞膜电位,增加细胞通透性,增强Ca2+-ATP酶活性。结论DHA-SMEDDS制备工艺简单,外观良好,乳化效率高,有望提高DHA的口服生物利用度。Objective To study the formulation and preparation technology of dihydroartemisinin self-microemulsion drug delivery system(DHA-SMEDDS)and evaluate it.Methods The formulation of DHA-SMEDDS was screened by solubility test,oil phase with emulsifier and co-emulsifier compatibility experiment and pseudo ternary phase diagram drawing.Taking the mean particle size and drug loading as evaluation indexes,the formulation was optimized by central composite design-response surface methodology,and the physicochemical properties and initial stability of DHA-SMEDDS were evaluated.The mechanism of promoting infiltration of DHA-SMEDDS in MDCK cell model was investigated.Results In the optimized DHA-SMEDDS formulation,the oil phase was caprylic capric triglycerride(15%),the emulsifier was polyoxyethylene 40 castor oil(46.4%),the mixed co-emulsifier was anhydrous ethanol(24.12%)and polyethylene glycol 400(14.48%).The prepared self-microemulsion had uniform and transparent appearance.The average particle size after self-emulsification was(24.55±0.18)nm,PDI was(0.092±0.028),potential was(-3.16±0.14)mV,the drug loading was(9.64±0.01)mg/g,the entrapment efficiency was(99.67±0.10)%,and emulsifying time was(13.90±0.10)s.Preliminary stability experiments showed that DHA-SMEDDS should be stored at low temperature and away from light.DHA-SMEDDS can open tight junction proteins between cells,decrease cell membrane potential,increase cell permeability,and enhance Ca2+-ATPase activity.Conclusion DHA-SMEDDS has the advantages of simple preparation process,good appearance and high emulsifying efficiency,which is expected to improve the oral bioavailability of DHA.

关 键 词：双氢青蒿素 自微乳给药系统 伪三元相图 星点设计-效应面法 质量评价 溶解度 促渗机制 生物利用度 

分 类 号：R283.6[医药卫生—中药学]