Paclitaxel tumor biodistribution and efficacy after intratumoral injection of a biodegradable extended release implant

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Abstract

Purpose:

The aim of this study was to investigate the effectiveness of paclitaxel controlled release from intratumorally injected polymer.

Methods:

The effectiveness of paclitaxel–polymer formulation injected intratumorally was tested in mouse bladder tumor model. To determine paclitaxel biodistribution in tumor at predetermined time periods the tumor was excised, frozen and sectioned, and the paclitaxel concentrations were determined in the tumor tissue and in plasma by HPLC. Histopathological evaluation of the necrosis and inflammation was performed on tumor sections.

Results:

In the paclitaxel/polymer group mice were injected intratumorally with 0.2 ml of the 10% (w/w) paclitaxel formulation, the tumor disappeared completely 5 days after injection, and mice survived till the end of the study (50 days post-tumor cells inoculation). In biodistribution studies, the highest paclitaxel concentration in the tumor tissue was 40 μg/mg 1 day after the intratumoral injection and decreased gradually during 10 days to 5 μg/mg that is still high enough to induce cytotoxic effect, and the necrotic effect of paclitaxel on the tumors was confirmed by histopathology.

Conclusions:

Treatment with local injection of polymer–paclitaxel formulation inhibited the growth of solid tumors. Distribution studies of paclitaxel after intratumoral injection showed high and effective drug concentrations in tumor.

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