Albendazole-cyclodextrin complex: enhanced cytotoxicity in ovarian cancer cells.

Abstract

BACKGROUND:

Over recent years, we have identified a potentially new indication for albendazole (ABZ) namely that of an anticancer agent. Our recent data indicate that besides regional use, the drug is quite likely to be useful as a systemic anticancer agent. However, with extremely low solubility, ABZ has to be prepared in a biocompatible solubilized form before any systemic evaluation is possible. The present study aimed at preparing soluble ABZ and evaluating its in vitro antiproliferative efficacy and toxicity.

EXPERIMENTAL DESIGN:

Using beta-cyclodextrins (CDs), various formulations of ABZ were prepared and tested in cell culture for antiproliferative efficacy, cell integrity and cell toxicity against human ovarian cancer cell lines 1A9, OVCAR-3 and SKOV-3. Hepatocytes isolated from patients undergoing liver tumor resection were used for toxicity evaluations.

RESULTS:

Treatment of tumor cells with ABZ-CD + citric acid (CA) solution led to dose-dependent inhibition of cell proliferation. Compared to an ethanolic solution of ABZ, ABZ-CD + CA increased the antiproliferative efficacy of ABZ. Furthermore, in contrast to the ethanolic solution, ABZ-CD-CA complex profoundly (p<0.001) reduced the number of OVCAR-3 colonies formed. Fresh human hepatocytes exposed for 3 days to the highest ABZ concentration used in the study (1 microM), revealed no drug toxicity.

CONCLUSION:

Complexation of ABZ with beta-cyclodextrin leads to the formation of an ABZ solution with potent antiproliferative effects. This solution may find clinical value as an intravenous anticancer agent.

• Authors: Mohammad H Pourgholami, Kiran T Wangoo, David L Morris
• Journal: Anticancer research (Anticancer Res) 2008 Sep-Oct Vol. 28 Issue 5A Pg. 2775-9 ISSN: 0250-7005 [Print] Greece
• PMID: 19035309 (Publication Type: Journal Article)

Chemical References

• Biocompatible Materials
• beta-Cyclodextrins
• Albendazole

Topics

• Albendazole (administration & dosage, chemistry, toxicity)
• Biocompatible Materials (administration & dosage, chemistry, toxicity)
• Cell Line, Tumor
• Female
• Hepatocytes (drug effects)
• Humans
• Ovarian Neoplasms (drug therapy)
• Solubility
• beta-Cyclodextrins (administration & dosage, chemistry, toxicity)