Antitumor characteristics of methoxypolyethylene glycol-poly(DL-lactic acid) nanoparticles containing camptothecin.
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 x 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.
Miura
Hidetaka
H
Department of Drug Delivery Research, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
Onishi
Hiraku
H
Sasatsu
Masanaho
M
Machida
Yoshiharu
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002166:Camptothecin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019344:Lactic Acid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D049329:Nanostructures; D011092:Polyethylene Glycols / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012510:Sarcoma 180 / Q000188:drug therapy / Q000378:metabolism
D000970:Antineoplastic Agents; D019344:Lactic Acid; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D002166:Camptothecin