载阿霉素纳米粒温敏凝胶的制备及评价  

Preparation and evaluation of doxorubicin-loaded nanoparticles thermosensitive gel

作　　者：杜华康 陆苑[1] 金阳 陈玉颖 王永林 李勇军[2,3] 刘文 DU Huakang;LU Yuan;JIN Yang;CHEN Yuying;WANG Yonglin;LI Yongjun;LIU Wen(Guizhou Provincial Key Laboratory of Pharmaceutics&State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University,Guiyang 550004,Guizhou,China;School of Pharmacy,Guizhou Medical University,Guiyang 550004,Guizhou,China;Engineering Research Center for the Development and Application of Ethnic Medicine and TCM of Ministry of Education,Guizhou Medical University,Guiyang 550004,Guizhou,China)

机构地区：[1]贵州医科大学贵州省药物制剂重点实验室&省部共建药用植物功效与利用国家重点实验室,贵州贵阳550004 [2]贵州医科大学药学院,贵州贵阳550004 [3]贵州医科大学贵州医科大学民族药与中药开发应用教育部工程研究中心,贵州贵阳550004

出　　处：《贵州医科大学学报》2024年第1期71-79,共9页Journal of Guizhou Medical University

基　　金：中央引导地方科技专项项目(黔科中引地[2018]4006);贵州省科技计划项目(黔科合平台人才[2016]5613/5677)。

摘　　要：目的 对制备出可用于肝动脉化疗栓塞(TACE)的载阿霉素纳米粒温敏凝胶(DOX-NPs-Gel)复合体系的相关特性进行评价。方法 以乳酸-羟基乙酸共聚物(PLGA)为载体,采用复乳法制备载阿霉素纳米粒(DOX-NPs),考察其外观、粒径、PDI和Zeta电位,经冷冻干燥得DOX-NPs冻干粉,将其分散于壳聚糖(CS)/β-甘油磷酸(β-GP)温敏凝胶(Gel),制得DOX-NPs-Gel;采用倒瓶法考察Gel、DOX-Gel、空白-NPs-Gel及DOX-NPs-Gel在37℃下的胶凝化时间及胶凝温度;扫描电镜观察微观结构;通过兔耳中动脉栓塞实验考察了空白-NPs-Gel的栓塞性能;通过在皮下注射空白-NPs-Gel于不同时间脱颈死小鼠,剥离出空白-NPs-Gel,测量其大小及质量,评价其吸收特性;采用动态膜透析法考察DOX、DOX-NPs、DOX-Gel的体外释放;采用无膜溶出法考察DOX-NPs-Gel的体外释放。结果 制备出的DOX-NPs形态规则,粒径为(186.68±5.99)nm,多分散系数(PDI)为(0.17±0.01),Zeta电位为(-23.33±1.54)mV,包封率和载药量分别为(77.10±4.46)%和(2.64±0.19)%;DOX-NPs-Gel 37℃下胶凝化时间为(165±15)s,胶凝化温度为(34.67±0.47)℃,冻干后其微观结构为整齐紧密的多孔结构;该复合体系可顺利通过微导管注射,可栓塞兔耳中动脉,且在皮下可被缓慢吸收;体外释放结果显示,第7天时DOX-NPs-Gel中DOX和DOX-NPs的释放率分别为(6.15±0.19)%和(47.25±5.11)%。结论 本研究制备的DOX-NPs-Gel在体温下可快速胶凝、可栓塞血管和皮下吸收,能够缓慢释放DOX-NPs。Objective To investigate related characteristics of doxorubicin-loaded nanoparticles thermosensitive gel(DOX-NPs-Gel)composite system for hepatic arterial chemoembolization(TACE).Methods Poly-lactic-co-glycolic acid(PLGA)as the carrier,doxorubicin-loaded nanoparticles(DOX-NPs)were prepared by double emulsion.The appearance,particle size,PDI and Zeta potential were investigated;DOX-NPs lyophilized powder was obtained,which was dispersed in chitosan(CS)/β-glycerophosphate(β-GP)thermosensitive gel(Gel)for DOX-NPs-Gel.Its gelling time and gelling temperature of Gel,DOX-Gel,Blank-NPs-Gel and DOX-NPs-Gel were examined by bottle-tumbling assay un the temperature of 37℃;microstructure was observed by scanning electron microscope;embolism function of Blank-NPs-Gel was investigated by Rabbit Ear Central Artery Embolism Experiment;subcutaneous injection of Blank-NPs-Gel was administered for mice death by neck dislocation at varied time points,then Blank-NPs-Gel was stripped for measurement and quality in order to evaluate its absorption features.Dynamic membrane dialysis was adopted to examine in vitro release of DOX,DOX-NPs,DOX-Gel;non-membrane dissolution assay was adopted to examine invitro release of DOX-NPs-Gel.Results The prepared DOX-NPs were morphologically regular,with a particle size of(186.68±5.99)nm,PDI of(0.17±0.01),Zeta potential of(-23.33±1.54)mV,encapsulation rate and drug load of(77.10±4.46)%and(2.64±0.19)%.The gelling time of DOX-NPs-Gel at 37℃was(165±15)s;gelling temperature was(34.67±0.47)℃.After lyophilization,its microstructure is neat and tightly porous.The composite system could be successfully injected through a microcatheter,which could successfully embolize the rabbit ear central artery and could be slowly absorbed subcutaneously.In vitro release results showed that the release rates of DOX and DOX-NPs in DOX-NPs-Gel at 7 th days were(6.15±0.19)%and(47.25±5.11)%.Conclusion The DOX-NPs-Gel prepared in this study can be rapidly gelling,embolizing blood vessels and be absorbed subcut

关 键 词：肝动脉化疗栓塞 温敏凝胶 纳米粒 阿霉素 缓释制剂 体外释放 

分 类 号：R943[医药卫生—药剂学]