载阿霉素pH敏感复合胶束的制备及体内药动学  

Doxorubicin loaded pH-sensitive copolymer mixed micelles:preparation and pharmacokinetic study in rats

作　　者：贾莉[1,2] 高岩[2] 马晶晶 乔明曦[2] JIA Li;GAO Yan;MA Jingjing;QIAO Mingxi(Heze Medical College,Heze 274000,China;School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]菏泽医学专科学校,山东菏泽274000 [2]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2020年第11期968-974,共7页Journal of Shenyang Pharmaceutical University

基　　金：国家自然科学基金资助项目(81573372)。

摘　　要：目的以pH敏感聚组氨酸-聚乳酸羟基乙酸-聚乙二醇-聚乳酸羟基乙酸-聚组氨酸嵌段共聚物(polyhistidine-b-poly(dl-lactide-co-glycolide-b-ethylene glycol-b-dl-lactide-co-glycolide)-b-polyhistidine,HPPPH)和单甲醚聚乙二醇-聚乳酸羟基乙酸嵌段共聚物(methoxy-poly(ethylene glycol)-poly(dl-lactide),MPP)为载体,制备pH敏感复合胶束,研究其理化性质和大鼠体内药物动力学。方法采用酸碱滴定法、芘荧光探针法、透析法、LC-MS/MS等方法研究复合胶束的体内外性质。结果HPPPH与MPP质量比为8∶2时制备的复合胶束稳定性较好,载阿霉素pH敏感复合胶束为壳核结构,平均粒径为89.0 nm,体外释放具有明显的pH敏感性和缓释效果;大鼠药物动力学结果表明,复合胶束可显著延长其在血液中的循环时间。结论与单一HPPPH胶束相比,复合胶束显著提高胶束稳定性,pH敏感复合胶束作为抗肿瘤药物递送系统具有广阔的应用前景。Objective To prepare novel pH-sensitive doxorubicin-loaded mixed micelles with pH sensitive copolymer polyhistidine-b-poly(dl-lactide-co-glycolide-b-ethylene glycol-b-dl-lactide-co-glycolide)-b-polyhistidine(HPPPH)and diblock copolymer methoxy poly(ethyleneglycol)-block-poly(dl-lactide-co-glycolide)(MPP),to study their vitro properties and pharmacokinetics in rats.Methods The in vitro and in vivo properties of the micelles were determined by acid-base titration,pyrene fluorescence probe,dialysis methods and HPLC-MS/MS.Results pH-sensitive mixed micelles have good stability when HPPPH/MPP was 8:2.Dox-loaded mixed micelles were core-shell structure and the mean particle size was 89.0 nm.They had obvious pH sensitivity and sustained release effect.The mixed micelles had a longer circulation in blood circulation and had better tumor targeting.Conclusion Compared with HPPPH micelles,HPPPH/MPP micelles significantly improve the stability.The pH-sensitive mixed micelles are expected to be promising antitumor drug delivery systems.

关 键 词：PH敏感 复合胶束 阿霉素 药动学研究 

分 类 号：R917[医药卫生—药物分析学]