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Repositioning of Anti-parasitic Drugs in Cyclodextrin Inclusion Complexes for Treatment of Triple-Negative Breast Cancer

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Abstract

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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Acknowledgements

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.

Funding

This study received financial support from the Universidad Nacional de Rosario and CONICET (Project N° PIP 112-201001-00194) and “Instituto Nacional del Cáncer.”

Author information

Author notes

  1. Josefina Priotti and María Virginia Baglioni contributed equally to this work.

Authors and Affiliations

  1. IQUIR-CONICET, Suipacha 570, 2000, Rosario, Argentina

    Josefina Priotti, Darío Leonardi & María Celina Lamas

  2. Instituto de Genética Experimental, Facultad de Ciencias Médicas, UNR, 2000, Rosario, Santa Fe, Argentina

    María Virginia Baglioni, María José Rico & Mauricio Menacho Márquez

  3. Departamento de Farmacia, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Suipacha 570, 2000, Rosario, Argentina

    Agustina García, Darío Leonardi & María Celina Lamas

  4. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario (IIDEFAR, UNR-CONICET), UNR, Ocampo y Esmeralda, 2000, Rosario, Argentina

    Mauricio Menacho Márquez

Authors
  1. Josefina Priotti
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  2. María Virginia Baglioni
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Corresponding author

Correspondence to María Celina Lamas.

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All experiments were performed in accordance with the Canadian Council on Animal Care guidelines.

Animal Studies

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

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