RT Journal Article
SR Electronic
T1 Albendazole-Cyclodextrin Complex: Enhanced Cytotoxicity in Ovarian Cancer Cells
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2775
OP 2779
VO 28
IS 5A
A1 POURGHOLAMI, MOHAMMAD H.
A1 WANGOO, KIRAN T.
A1 MORRIS, DAVID L.
YR 2008
UL http://ar.iiarjournals.org/content/28/5A/2775.abstract
AB 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 β-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 μM), revealed no drug toxicity. Conclusion: Complexation of ABZ with β-cyclodextrin leads to the formation of an ABZ solution with potent antiproliferative effects. This solution may find clinical value as an intravenous anticancer agent.