Antitumor effect of the paclitaxel-eluting membrane in a mouse model.

Abstract

Local treatment of primary bile duct cancer, which grows locally at the primary lesion and seldom metastasizes to distant sites, is challenging. The present study evaluated the antitumor effect, systemic toxicity, biodistribution and survival benefit of the paclitaxel-eluting polyurethane membrane in a tumor model. Membranes containing various amounts of paclitaxel (0, 100, 300, 600 and 1,200 µg/disc) were inserted beneath the tumor mass in mouse models. Tumor size and body weight of the tumor models were monitored for 26 days after insertion of the membrane. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay was performed in the tumor tissues. High-performance liquid chromatography was performed for evaluation of paclitaxel concentration in peripheral tissues. Tumor volumes on day 26 of membrane treatment were decreased in a dose-dependent manner. No significant difference in body weight was observed in the groups. A greater number of apoptotic cells were counted per high power field in tumor tissues following an increase of paclitaxel concentration. In the 1,200 µg-group, concentrations of paclitaxel were significantly higher in tumors compared with those of other tissues and serum. The paclitaxel-eluting membrane demonstrated a significant and dose-dependent antitumor activity, and did not exert systemic toxicity in the tumor model.