羟基喜树碱修饰纳米粒的制备及药动学研究

 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 95 nm ，多分散指数 PDI=0.146 ， Zeta 电位为 - 15.9 mV ；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， 0.5 h 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： <> t _1/2α 分别为 0.16 和 0.32 h ， <> t _1/2β 分别为 0.51 和 6.26 h ， <> V _(c) 分别为 0.28 和 0.66 L·kg^-1 ， <> CL _(s) 分别为 0.75 和 0.19 L·h^-1·kg^-1 ， AUC 分别为 3.34 和 12.87 mg·h·L^-1 。 结论 羟基喜树碱纳米粒具有缓释和长循环作用。

Preparation and Pharmacokinetics of HCPT/MePEG-PIOCA Nanoparticles

OBJECTIVE To prepare hydroxycamptothecin (HCPT) loaded nanoparticles with methoxy poly(ethylene glycol)-poly(isooctyl cyanoacrylate) and to investigate the pharmacokinetic characteristics. METHODS HCPT/MePEG-PIOCA nanoparticles were formed by nanoprecipitation method. The morphology was observed by transmission electron microscope. Laser particle size analyzer was used to detect the particle size and Zeta potential. The encapsulation efficiency, drug loading rate and in vitro cumulative release rate were evaluated by UV-Vis spectrophotometry.The high-performance liquid chromatography (HPLC) was used to detect and compare the pharmacokinetic parameters of HCPT injection and HCPT/MePEG-PIOCA nanoparticles in plasma of mice. RESULTS Using the transmission electron microscope, HCPT/MePEG-PIOCA nanoparticles exhibited a spherical shape and the distribution was uniform. The average particle size , polydispersity index and Zeta potential were 95 nm,0.146 and -15.9 mV, respectively. The encapsulation efficiency and drug loading rate were 72.9% and 11.31%. The release rate in vitro was composed of abrupt release and sustained release, and the release rate in 0.5h was 21%. The main pharmacokinetic parameters of HCPT injection and HCPT／MePEG-PIOCA nanoparticles were as follows: t1/2α 0.16 and 0.32 h, t1/2β 0.51 and 6.26 h, V(c) 0.28 and 0.66 L·kg-1，CL(s) 0.75 and 0.19 L·h-1·kg-1，AUC 3.34 and 12.87 mg·h·L-1。CONCLUSION HCPT／MePEG-PIOCA nanoparticles showed the qualities of sustained-release and long-circulation compared with HCPT injection.