载紫杉醇的PEG修饰的大黄酸偶联物胶束的表征、体外释放及药动学研究  

Characterization,in Vitro Release and Pharmacokinetics of Paclitaxel-loaded PEGylated Carboxymethyl Chiosan-Rhein Conjugate Micelles

作　　者：郑雅玲 王夏英 许雪雅 林亚娟 徐伟[1] 王晓颖[1] ZHENG Yaling;WANG Xiaying;XU Xueya;LIN Yajuan;XU Wei;WANG Xiaoying(Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)

机构地区：[1]福建中医药大学,福州350122

出　　处：《中国现代应用药学》2023年第7期865-872,共8页Chinese Journal of Modern Applied Pharmacy

基　　金：国家自然科学基金项目(81603301);福建省科技厅引导性项目(2020Y0050)。

摘　　要：目的对载紫杉醇(paclitaxel,PTX)的聚乙二醇修饰的大黄酸偶联物[PEGylatedcarboxymethylchiosan-rhein conjugate(polymeric),PTX/CRmP]胶束进行形态与结构表征,考察其体外(模拟血液环境中)释放情况及药动学特征。方法通过透射电镜(transmission electron microscopy,TEM)、差示扫描量热法(differential scanning calorimetry,DSC)、X射线衍射(X-ray diffraction,XRD)对胶束的粒径、形态及结构等方面进行评价;在pH 7.4磷酸盐缓冲液(含0.8 mol·L^(-1)水杨酸钠)中进行PTX/CRmP胶束的体外释放研究,计算PTX的累积释放率,绘制累积释放曲线;以大鼠为模型,尾静脉注射PTX/CRmP胶束后,通过药-时曲线、药动学参数等对其进行药动学研究。结果TEM显示PTX/CRmP胶束呈类球形,粒径约160 nm,分布均匀;DSC和XRD显示PTX几乎全部被CPmP胶束包载入其内核中。PTX/CRmP胶束在pH7.4磷酸盐缓冲液(含0.8 mol·L^(-1)水杨酸钠)中24 h内累积释放率为92.2%,药物释放速率显著慢于Taxol■。药动学研究表明,与Taxol?组相比,PTX/CRmP胶束中药物的分布和消除较慢,药-时曲线下面积显著增加,CRmP胶束能延长PTX半衰期及其在血液循环系统中的循环时间。结论CRmP偶联物物理包载PTX于内核中所得的PTX/CRmP胶束,粒径小,在体外模拟血液pH环境中缓释,PTX生物利用度提高。OBJECTIVE To characterize the morphology and structure of PEGylated carboxymethyl chiosan-rhein conjugate(polymeric)micelles loaded with paclitaxel(PTX)(PTX/CRmP micelles),and to investigate the release in vitro and pharmacokinetic characteristics of PTX/CRmP micelles.METHODS Transmission electron microscopy(TEM),differential scanning calorimetry(DSC),X-ray diffraction(XRD)were used to evaluate the particle size,morphology and structure of micelles.The in vitro release of PTX/CRmP micelles was studied in pH 7.4 phosphate buffer solution(containing 0.8 mol·L^(-1) sodium salicylate)to calculate the cumulative release rate of PTX and draw the cumulative release curve.The pharmacokinetics of PTX/CRmP micelles were studied by concentration-time curve and pharmacokinetic parameters after they were injected into the tail vein of rats.RESULTS TEM showed that PTX/CRmP micelles were spherical,with a particle size of about 160 nm and uniform distribution.DSC and XRD showed that PTX was almost all loaded into the core of CPmP micelles.The cumulative release of PTX/CRmP micelles in pH 7.4 PBS(containing 0.8 mol·L^(-1) sodium salicylate)was 92.2% within 24 h,significantly slower than that of Taxol■.In pharmacokinetic studies,drug distribution and elimination in PTX/CRmP micelles group were slower and AUC was enhanced.The CRmP micelles could prolong the half-life and circulation time of PTX in the blood circulation system.CONCLUSION PTX/CRmP micelles are obtained by physically encapsulating PTX in the cores of CRmP micelles,with a small particle size and slow PTX release in the simulated blood pH environment in vitro.The bioavailability of PTX is improved.

关 键 词：聚合物胶束 大黄酸偶联物 紫杉醇 体外释放 药动学 

分 类 号：R943[医药卫生—药剂学]