Drug repositioning refers to the identification of new therapeutic indications for drugs already approved. Albendazole and ricobendazole have been used as anti-parasitic drugs for many years; their therapeutic action is based on the inhibition of microtubule formation. Therefore, the study of their properties as antitumor compounds and the design of an appropriate formulation for cancer therapy is an interesting issue to investigate. The selected compounds are poorly soluble in water, and consequently, they have low and erratic bioavailability. In order to improve their biopharmaceutics properties, several formulations employing cyclodextrin inclusion complexes were developed. To carefully evaluate the in vitro and in vivo antitumor activity of these drugs and their complexes, several studies were performed on a breast cancer cell line (4T1) and BALB/c mice. In vitro studies showed that albendazole presented improved antitumor activity compared with ricobendazole. Furthermore, albendazole:citrate-β-cyclodextrin complex decreased significantly 4T1 cell growth both in in vitro and in vivo experiments. Thus, new formulations for anti-parasitic drugs could help to reposition them for new therapeutic indications, offering safer and more effective treatments by using a well-known drug.
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J.P. and M.V.B. are grateful to CONICET for Doctoral Fellowships. The authors also thank Ferromet S.A. (agent of Roquette in Argentina) for their donation of β-CD.
This study received financial support from the Universidad Nacional de Rosario and CONICET (Project N° PIP 112-201001-00194) and “Instituto Nacional del Cáncer.”
All experiments were performed in accordance with the Canadian Council on Animal Care guidelines.
All institutional and national guidelines for the care and use of laboratory animals were followed. This study was authorized by the Ethics Committee for Animal Use (registration number 1659/2016).
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Priotti, J., Baglioni, M.V., García, A. et al. Repositioning of Anti-parasitic Drugs in Cyclodextrin Inclusion Complexes for Treatment of Triple-Negative Breast Cancer. AAPS PharmSciTech 19, 3734–3741 (2018). https://doi.org/10.1208/s12249-018-1169-y
- breast cancer cell line