肝靶向羟基喜树碱缓释毫微粒的研究

采用吸附—包裹法制备了聚乙烯吡啶烷酮包被的羟基喜树碱聚氰基丙烯酸正丁酯毫微粒。研究了该毫微粒的形态、粒径及粒径分布、载药量、体外释药特征、动物体内的分布与药代动力学参数。结果表明平均粒径dav=81.2nm,载药量为1.22%,体外释药速率符合Higuchi方程:Q=0.0615+0.0940t,静脉注射后15min,即有68.2%羟基喜树碱浓集于肝脏。血浆药浓—时间曲线符合二室开放药动学模型。主要药动学参数为:Vc=3.548L,T_1/2β=146.99h,CL=0.1788L·h^-1。说明该载药毫微粒具有明显的肝靶向和缓释作用。本文报道的吸附─包裹法对水、脂不溶性药物聚氰基丙烯酸酯毫微粒的制备具有一定参考价值。

STUDY ON LIVER TARGETING AND SUSTAINED RELEASE HYDROXYCAMPTOTHECIN POLYBUTYLCYANOACRYLATE NANOPARTICLES

The liver targeting and sustained release hydroxycamptothecin polybutylcyanoacrylate nanoparticles (HCPT-PBCA-NP) which were wrapped up with ployvinylpyrrolidone(PVP) were prepared by adsorption-enwrapping method. The morphology, size and size distribution, drug loading, release characteristics in vitro, distribution and pharmacokinetic parameters in animals of the PVP-HCPT-PBCA-NP were studied. The results showed that the average diameter was 81.2 nm, drug loading was 1.22%. The release characteristics in vitro was in accord with Higuchi equation: Q = 0.0615 + 0.0940 square root of t.64.5% of the HCPT were concentrated in liver 15 min after iv PVP-HCPT-PBCA-NP. The plasma drug concentration-time curve of the HCPT in 5 rabbits was fitted to a two-compartment open model. The Vc was 3.548 L; T1/2 was 146.99 h; CL was 0.178 L.h-1. The method of preparation presented in this paper seems to have important reference value for the preparation of PBCA-NP of the insoluble drugs both in water and in oil.