文献类型：期刊文献

中文题名：漆酚基BPAU-NH2 -Gal紫杉醇载药胶束的pH响应性及其体外性能

英文题名：pH Responsiveness and Their in vitro Properties of Urushiol-based BPAU-NH2-Gal Paclitaxel-loaded Micelle

作者：齐志文[1] 周昊[1] 陈虹霞[1] 张昌伟[1] 邓涛[2] 王成章[1]

第一作者：齐志文

机构：[1]中国林业科学研究院林产化学工业研究所,生物质化学利用国家工程实验室,国家林业和草原局林产化学工程重点实验室,江苏省生物质能源与材料重点实验室,江苏省林业资源高效加工利用协同创新中心,江苏南京210042;[2]广州中医药大学热带医学研究所,广东广州510405

年份：2020

卷号：40

期号：5

起止页码：121-128

中文期刊名：林产化学与工业

外文期刊名：Chemistry and Industry of Forest Products

收录：CSTPCD;;Scopus;北大核心:【北大核心2017】；CSCD:【CSCD2019_2020】；

基金：国家重点研发计划资助项目(2017YFD0601305);江苏省生物质能源与材料重点实验室基本科研业务费(JSBEM-201608)。

语种：中文

中文关键词：漆酚;载药胶束;紫杉醇;pH响应型;HepG2

外文关键词：urushiol;drug-loaded micelles;paclitaxel;pH-responsive;HepG2

分类号：TQ35

摘要：以5-氨基-1-戊醇(P)、1,4-丁二醇二丙烯酸酯(BUDA)和胺基官能化甲氧基聚乙二醇(mPEG-NH 2)为原料,通过自组装方法合成了传统pH敏感型胶束BUDA-P(mPEG-NH 2)(BPAU);再以三烯漆酚苯硼酸胺衍生物(URU-NH 2)为疏水单元,半乳糖(Gal)为识别单元,合成了pH敏感型纳米胶束BPAU-NH 2-Gal。以紫杉醇(PTX)为受试药物,采用透析法制备了纳米载药胶束(PTX@BPAU-NH 2-Gal)。通过核磁共振(NMR)、凝胶色谱(GPC)、表面张力、Zeta电位分析对胶束的结构、重均相对分子质量(M w)、临界胶束浓度(CMC)、Zeta电位进行了表征,采用透射电镜(TEM)表征载药胶束的形貌,动态光散射法(DLS)测定了其粒径。采用高效液相色谱(HPLC)法测定了胶束对PTX的包封率和载药量,动态膜透析法考察了载药胶束在体外不同pH值条件下的释放特性和HepG2细胞摄入性能。研究结果表明:漆酚BPAU-NH 2-Gal胶束已经成功合成,胶束BPAU-NH 2-Gal的M W值约为15550,分散指数(PDI)为1.49,CMC值约为90.29 mg/L,Zeta电位值为29.7 mV。载药胶束PTX@BPAU-NH 2-Gal外观呈不规则椭圆结构,平均粒径为195 nm左右;对紫杉醇的包封率为92.51%,载药量为31.76%;在pH值4.5时,其药物释放量明显高于其在pH值为6.8、7.4时的药物释放量,具有明显的pH响应性;该载药胶束表现出对人体正常肝细胞LO2的低毒性,胶束质量浓度为200 mg/L时,LO2细胞存活率仍大于93%;在pH值4.5条件下,人肝癌细胞HepG2对该载药胶束具有很强的摄入能力。
pH-sensitive micelles BUDA-pentanolamine-(mPEG-NH 2)(BPAU)were synthesized with traditional pH-sensitive micelle materials 5-amino-1-pentanol(pentanolamine),1,4-butanediol diacrylate(BUDA)and amino group functionalization methoxypolyethylene glycol(mPEG-NH 2)as raw materials by self-assembly.Then,with trieneurushiol phenol borate derivative(URU-NH 2)as the hydrophobic unit and galactose(Gal)as the recognition unit,the pH-sensitive BPAU-NH 2-Gal nanomicelle was synthesized.And then,Paclitaxel(PTX)was used as the test drug,and nano-drug loaded micelles(PTX@BPAU-NH 2-Gal)were prepared by dialysis.By nuclear magnetic(NMR),gel chromatography(GPC),surface/interfacial tension,Zeta potential analysis,micelle structure,average relative molecular mass(M w)and critical micelle concentration(CMC),Zeta potential were characterized.The morphology of drug-loaded micelles was characterized by TEM,and the particle size was determined by DLS.High-performance liquid chromatography(HPLC)was used to determine the encapsulation efficiency and drug loading quantity of PTX.Dynamic membrane dialysis was used to investigate the release and uptake characteristics of drug-loaded micelles at different pH values in vitro.The results showed that BPAU-NH 2-Gal was synthesized successfully,and the M w value of micelle BPAU-NH2-Gal was about 15550,dispersion index(PDI)was 1.49,the CMC value was about 90.29 mg/L,and the Zeta potential value was 29.69 mV.The drug-loaded micelle PTX@BPAU-NH 2-Gal had an irregular elliptical structure with the average particle size about 195 nm;the encapsulation rate of paclitaxel was 92.51%,the drug load quantity was 31.76%.When the pH value was 4.5,the release rate was significantly higher than that in the environment with pH value of 6.8 and 7.4,and the micelle release had obvious pH responsiveness property.When the pH value of the buffer solution was 4.5,6.8,and 7.4,the cumulative release rate of paclitaxel from the drug-loaded micelle within 90 h were 50.00%,34.26%and 9.00%,respectively,which showed low toxicity to LO2 and high activity against HepG2.