Paclitaxel tumor biodistribution and efficacy after intratumoral injection of a biodegradable extended release implant.
OBJECTIVE
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 microg/mg 1 day after the intratumoral injection and decreased gradually during 10 days to 5 microg/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.
Shikanov
Ariella
A
Department of Medicinal Chemistry and Natural Products, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel. ariellashikanov@gmail.com
Shikanov
Sergey
S
Vaisman
Boris
B
Golenser
Jacob
J
Domb
Abraham J
AJ
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D002470:Cell Survival; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003652:Decanoic Acids; D004354:Drug Screening Assays, Antitumor; D005260:Female; D007267:Injections; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011108:Polymers; D012277:Ricinoleic Acids
D000972:Antineoplastic Agents, Phytogenic; D003652:Decanoic Acids; C493322:Poly(sebacic acid-co-ricinoleic acid); D011108:Polymers; D012277:Ricinoleic Acids; D017239:Paclitaxel