ANTITUMOR EFFICACY AND BIODISTRIBUTION OF INTRAVENOUS POLYMERIC MICELLAR PACLITAXEL

The purpose of this study was to evaluate the diblock copolymer poly(D L-lactide)-block-methoxy polyethylene glycol as an i.v. delivery vehic le for paclitaxel. Nude mice were implanted s.c. with fragments of MV- 522 lung carcinomas and treated with paclitaxel on a daily x 5 schedul e when tumors were approximately 5 x 5 mm in size, Cremophor paclitaxe l or polymeric micellar paclitaxel were given i.p. or i.v. at the maxi mum tolerated dose (Cremophar paclitaxel MTD: 20 mg/kg/day i.v. or i.p .; micellar paclitaxel MTD: 25 mg/kg/day i.v. or 100 mg/kg/day i.p.). The tumors were measured using callipers during the experiment and acc urately weighted at the end. Two biodistribution studies were carried out. In one study, the nude mice were given micellar paclitaxel at a d ose of 25 mg/kg i.v. or 100 mg/kg i.p. In another study, BDF-1 mice we re given either micellar paclitaxel or Cremophor paclitaxel at a dose of 20 mg/kg i.v. The mice were sacrificed after a given time and the o rgans were harvested. Paclitaxel in the organs was extracted with acet onitrile and analyzed using HPLC. Tumor growth inhibitions of 98.5 and 98.7% were obtained from i.v. administered micellar paclitaxel and Cr emophor paclitaxel at their MTDs, respectively. Micellar paclitaxel wa s more efficacious i.p. (98.7% tumor growth inhibition) than Cremophor paclitaxel i.p. (83.0% tumor growth inhibition) al their MTDs. The hi ghest concentrations of paclitaxel were found in the liver after admin istration of paclitaxel formulations. Paclitaxel was also found in spl een, kidney, lung and blood, in order of decreasing concentration. The preliminary results indicate that polymeric micellar paclitaxel could be a clinically useful chemotherapeutic formulation.