Therapeutic effect of intravesical administration of paclitaxel solubilized with poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) in an orthotopic bladder cancer model.

Abstract

BACKGROUND:

To evaluate the effects of intravesical administration of paclitaxel (PTX-30W), which was prepared by solubilization with a water-soluble amphiphilic polymer composed of PMB30W, a copolymer of 2-methacryloyloxyethyl phosphorylcholine and n-butyl methacrylate, in an orthotopic bladder cancer model.

METHODS:

The cytotoxicities of PMB30W were examined in MBT-2 cell cultures and the results were compared with those of the conventional paclitaxel solubilizer Cremophor. In an orthotopic MBT-2 bladder cancer model, the effect of intravesical administration of PTX-30W was compared with that of paclitaxel solubilized with Cremophor (PTX-CrEL). The paclitaxel concentration in bladder tumors after the intravesical treatment was also evaluated using liquid chromatography tandem mass spectrometry (LC-MS/MS) system.

RESULTS:

In vitro, Cremophor exhibited dose-dependent cytotoxicity towards MBT-2 cells, whereas no cytotoxicity was observed with PMB30W. In the orthotopic bladder cancer model, intravesical administration of PTX-30W resulted in a significant reduction of bladder wet weight compared with that of PTX-CrEL. The paclitaxel concentration in bladder tumors after the intravesical treatment was significantly higher in PTX-30W treated mice than in PTX-CrEL treated mice.

CONCLUSIONS:

Intravesically administered PTX-30W can elicit stronger antitumor effects on bladder tumors than conventional paclitaxel formulated in Cremophor, presumably because of its better penetration into tumor cells. PTX-30W might be a promising antitumor agent for intravesical treatment of non-muscle invasive bladder cancer.

• Authors: Koetsu Tamura, Eiji Kikuchi, Tomohiro Konno, Kazuhiko Ishihara, Kazuhiro Matsumoto, Akira Miyajima, Mototsugu Oya
• Journal: BMC cancer (BMC Cancer) Vol. 15 Pg. 317 (Apr 26 2015) ISSN: 1471-2407 [Electronic] England
• PMID: 25928041 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Methacrylates
• Phosphorylcholine
• poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate)
• Paclitaxel

Topics

• Administration, Intravesical
• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, pharmacokinetics)
• Carcinoma, Transitional Cell (drug therapy, pathology)
• Cell Line, Tumor
• Drug Screening Assays, Antitumor
• Female
• Methacrylates (administration & dosage, pharmacokinetics)
• Mice, Inbred C3H
• Neoplasm Transplantation
• Paclitaxel (administration & dosage, pharmacokinetics)
• Phosphorylcholine (administration & dosage, analogs & derivatives, pharmacokinetics)
• Solubility
• Tumor Burden (drug effects)
• Urinary Bladder Neoplasms (drug therapy, pathology)