ABSTRACT
OBJECTIVE: To prepare amphiphilic long-circulating hydroxycamptothecin nanoparticles and investigate its physicochemical properties and pharmacokinetic characteristics in rats. METHODS: Polyethyleneglycol-polycaprolactone (PEG-PCL) was synthesized. HCPT-PEG-PCL-NPs were prepared by solvent-diffusion method using PEG-PCL block copolymer as the matrix. The obtained NPs were evaluated, and the physical stabilities of both suspl and freeze-dried powder were investigated. High-performance liquid chromatography (HPLC) was used to determine and compare the pharmacokinetic parameters of HCPT injection and HCPT-PEG-PCL-NPs prepared with different copolymers in rats. RESULTS: When using PEG4000-PCL1250, PEG4000-PCL2000, PEG2000-PCL1250, PEG2000-PCL2000 as the carrier materials, the average particle sizes of NPs were 110.0, 116.1, 99.1 and 119.9 nm; the Zeta potentials were -16.9, -22.4, -28.8 and -33.5 mV; the entrapment efficiency were 83.10%, 88.29%, 77.46% and 80.67%; and the drug loading percentages were 2.56%, 2.96%, 2.14% and 2.31%, respectively. The physical stability of the freeze-dried powder was better, and hot environment seemed to be bad for the stability. The t1/2s of HCPT-PEG4000-PCL1250-NPs, HCPT-PEG2000-PCL1250-NPs, HCPT-PEG4000-PCL2000-NPs and HCPT-PEG2000-PCL2000-NPs were 18.07, 9.08, 5.25 and 5.14 times longer than that of HCPT injection which was 0.1418 h. CONCLUSION: The HCPT-PEG-PCL-NPs show sustained-release effect and long-circulation property compared with HCPT injection. Copyright 2012 by the Chinese Pharmaceutical Association.