Preparation and Characterization of an Aqueous Suspension Containing Nanoparticles of Poly (DL-lactic Acid)/Irinotecan/Polyethylene Glycol Monostearate

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Poly (DL-lactic acid), irinotecan and polyethylene glycol monostearate were dissolved in acetone, and coprecipitated by the addition of water. Then, the organic solvent was evaporated. The nanoparticle-containing suspension (NP-S) obtained by that coprecipitation was characterized both in vitro and in vivo. The nanoparticles showed a mean diameter of 150nm with its distribution of 110 to 270nm. At least 20%(w/w) of the drug was incorporated in the nanoparticles. These particle characteristics of NP-S were reproducibly obtained. When the antitumor effect was examined by the i.v. administration at repeated doses of 20mg irinotecan eq./kg/day for 3 days (20×3mg irinotecan eq./kg) using mice bearing sarcoma 180 subcutaneously, NP-S was found to be significantly effective and it also tended to show a better suppression of tumor growth than an irinotecan hydrochloride (CPT-11) aqueous solution. After i.v. injections in rats, NP-S retained the plasma concentration of irinotecan longer than a CPT-11 aqueous solution. These findings suggest that NP-S may possibly improve the action of irinotecan against solid tumors.
2003-06-10