Mohammad H Pourgholami1, Kiran T Wangoo, David L Morris. 1. Cancer Research Laboratories, University of New South Wales Department of Surgery, St. George Hospital, Sydney, NSW 2217, Australia. mh.pourgholami@unsw.edu.au
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.
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 humanovarian 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: Robert J Mishur; Matthew E Griffin; Cooper H Battle; Bin Shan; Janarthanan Jayawickramarajah Journal: Bioorg Med Chem Lett Date: 2010-11-21 Impact factor: 2.823
Authors: Elisângela A M Mendonça; Mariane C B Lira; Marcelo M Rabello; Isabella M F Cavalcanti; Suely L Galdino; Ivan R Pitta; Maria do Carmo A Lima; Maira G R Pitta; Marcelo Z Hernandes; Nereide S Santos-Magalhães Journal: AAPS PharmSciTech Date: 2012-10-02 Impact factor: 3.246