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.
Key words
hydroxycamptothecin /
methoxy poly(ethylene glycol)-poly(isooctyl-cyanoacrylate) /
nanoparticles /
pharmacokinetics
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（ 收稿日期 ： 2009-07-31 ）
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