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目的制备包载羟基喜树碱(HCPT)的聚乙二醇单甲醚-聚氰基丙烯酸异辛酯(MePEG-PIOCA)纳米粒,并进行了质量评价,研究了其在小鼠体内的药动学。方法采用纳米沉析法制备HCPT/MePEG-PIOCA纳米粒;透射电镜观察纳米粒的形态;激光粒度分析仪检测粒径分布和Zeta电位;紫外可见分光光度法评价载药量、包封率及体外释药;高效液相色谱法检测并比较HCPT注射液和HCPT/MePEG-PIOCA纳米粒在小鼠体内的药动学参数。结果本法制备的HCPT/MePEG-PIOCA纳米粒呈球形,分布均匀;平均粒径为95nm,多分散指数PDI=0.146,Zeta电位为-15.9mV;包封率和载药量分别为72.9%和11.31%;体外释药由突释相和缓释相组成,0.5h的释放率为21%;HCPT注射液和HCPT/MePEG-PIOCA纳米粒的主要药动学参数为:t1/2α分别为0.16和0.32h,t1/2β分别为0.51和6.26h,V(c)分别为0.28和0.66L·kg-1,CL(s)分别为0.75和0.19L·h-1·kg-1,AUC分别为3.34和12.87mg·h·L-1。结论羟基喜树碱纳米粒具有缓释和长循环作用。
OBJECTIVE To prepare polyethylene glycol monomethyl ether-octyl polycyanoacrylate (MePEG-PIOCA) loaded with hydroxycamptothecin (HCPT) and to evaluate its quality. The effects of its drug in mice Dynamic. Methods The nanoparticles of HCPT / MePEG-PIOCA were prepared by nano-precipitation method. The morphology of nanoparticles was observed by transmission electron microscopy. The particle size distribution and Zeta potential were measured by laser particle size analyzer. The drug loading, encapsulation efficiency and in vitro Drug release was measured by HPLC. The pharmacokinetic parameters of HCPT injection and HCPT / MePEG-PIOCA nanoparticles in mice were detected by HPLC. Results The nanoparticles of HCPT / MePEG-PIOCA prepared by this method were spherical and uniform in distribution. The average particle diameter was 95 nm, the polydispersity index was 0.146 and the Zeta potential was -15.9 mV. The encapsulation efficiency and drug loading were 72.9% and 11.31%. The in vitro drug release consisted of a burst phase and a sustained-release phase with a release rate of 21% at 0.5h. The main pharmacokinetic parameters of HCPT injection and HCPT / MePEG-PIOCA nanoparticles were: t1 / 2α 0.16 And 0.32h, t1 / 2β were 0.51 and 6.26h, V (c) were 0.28 and 0.66L · kg-1, respectively, CL (s) were 0.75 and 0.19L · h-1 · kg- 3.34 and 12.87 mg · h · L -1. Conclusion Hydroxycamptothecin nanoparticles have slow release and long cycle.