Antitumor properties of irinotecan-containing nanoparticles prepared using poly(DL-lactic acid) and poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol).
Irinotecan-containing nanoparticles (NP) were prepared by coprecipitation with addition of water to acetone solution of poly(DL-lactic acid), poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) and irinotecan, and subsequent evaporation of organic solvent. NP were purified by gel filtration and used for experiments after condensation by evaporation. The obtained NP showed the drug content of 4.5% (w/w) and the mean particle diameter of 118 nm with the particle diameter distribution between 80-210 nm. When the antitumor effect was examined at a repeated dose of 20 mg irinotecan eq/kg for 3 d (3 x 20 mg/kg) using mice bearing Sarcoma 180 subcutaneously, only NP suppressed tumor growth significantly. After i.v. injection in rats, NP maintained irinotecan plasma concentration longer than CPT-11 aqueous solution. The present nanoparticle formation is suggested as a possibly useful dosage form of irinotecan against solid tumor.
Onishi
Hiraku
H
Department of Drug Delivery Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. onishi@hoshi.ac.jp
Machida
Yoshiaki
Y
Machida
Yoshiharu
Y
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000097:blood; D002166:Camptothecin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood; D004304:Dosage Forms; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000097:blood; D000077146:Irinotecan; D007773:Lactates / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008863:Microspheres; D036103:Nanotechnology / Q000379:methods; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012510:Sarcoma 180 / Q000188:drug therapy; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000972:Antineoplastic Agents, Phytogenic; D004304:Dosage Forms; D006131:Growth Inhibitors; D007773:Lactates; C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols; D000077146:Irinotecan; D002166:Camptothecin