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


METHODS
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.


CONCLUSIONS
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.
Pourgholami
Mohammad H
MH
Cancer Research Laboratories, University of New South Wales Department of Surgery, St. George Hospital, Sydney, NSW 2217, Australia. mh.pourgholami@unsw.edu.au
Wangoo
Kiran T
KT
Morris
David L
DL
D015766:Albendazole / Q000008:administration & dosage* / Q000737:chemistry* / Q000633:toxicity; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D005260:Female; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D012995:Solubility; D047392:beta-Cyclodextrins / Q000008:administration & dosage* / Q000737:chemistry* / Q000633:toxicity
D001672:Biocompatible Materials; D047392:beta-Cyclodextrins; D015766:Albendazole