Abstract
The novel nanoparticles (CPT-NP) were prepared by the solvent evaporation method using methoxypolyethylene glycol–poly(dl-lactic acid) block copolymer as a matrix and camptothecin (CPT) as an antitumor agent, and the antitumor characteristics were examined in vitro and in vivo. The mean diameter of CPT-NP was approximately 250 nm. The drug release from CPT-NP in phosphate-buffered saline, pH 7.4, depended on the particle concentration; in the diluted condition, the initial rapid release was greater and subsequent gradual release was faster. After i.v. administration (0.5 mg CPT eq./kg) in rats, CPT-NP showed a longer plasma retention than CPT solution. In both single (2.5 mg CPT eq./kg) and double (2.5 mg CPT eq./kg×2) administration to mice bearing sarcoma 180 solid tumor, CPT-NP were much more effective than CPT solution; especially, the tumor disappeared completely in three of the four mice in twice administration of CPT-NP, when the body weight did not decrease markedly. After i.v. administration to the tumor-bearing mice, CPT-NP showed better plasma retention, and high and long tumor localization. CPT-NP are suggested to greatly improve the efficacy of CPT due to their pharmacokinetic features.
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