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Drug repurposing for the treatment of alveolar echinococcosis: in vitro and in vivo effects of silica nanoparticles modified with dichlorophen

Published online by Cambridge University Press:  28 August 2019

Julia Fabbri ,
Patricia E. Pensel ,
Clara M. Albani ,
Valeria B. Arce ,
Daniel O. Mártire  and
María C. Elissondo Open the ORCID record for María C. Elissondo [Opens in a new window]
Julia Fabbri
Affiliation:
Laboratorio de Zoonosis Parasitarias, Instituto de Investigaciones en Producción, Sanidad y Ambiente (IIPROSAM), Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, Funes 3250, 7600, Mar del Plata, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
Patricia E. Pensel
Affiliation:
Laboratorio de Zoonosis Parasitarias, Instituto de Investigaciones en Producción, Sanidad y Ambiente (IIPROSAM), Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, Funes 3250, 7600, Mar del Plata, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
Clara M. Albani
Affiliation:
Laboratorio de Zoonosis Parasitarias, Instituto de Investigaciones en Producción, Sanidad y Ambiente (IIPROSAM), Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, Funes 3250, 7600, Mar del Plata, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
Valeria B. Arce
Affiliation:
Centro de Investigaciones Ópticas (CIOp), (CONICET La Plata – CIC – UNLP), Camino Parque Centenario e/505 y 508, Gonnet, Argentina
Daniel O. Mártire
Affiliation:
Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), CCT-La Plata-CONICET, Universidad Nacional de La Plata, Diagonal 113 y 64, CP 1900, La Plata, Buenos Aires, Argentina
María C. Elissondo*
Affiliation:
Laboratorio de Zoonosis Parasitarias, Instituto de Investigaciones en Producción, Sanidad y Ambiente (IIPROSAM), Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, Funes 3250, 7600, Mar del Plata, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
*
Author for correspondence: María C. Elissondo, E-mail: [email protected]
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Abstract

Alveolar echinococcosis is a neglected parasitic zoonosis caused by the metacestode Echinococcus multilocularis, which grows as a malignant tumour-like infection in the liver of humans. Albendazole (ABZ) is the antiparasitic drug of choice for the treatment of the disease. However, its effectiveness is low, due to its poor absorption from the gastro-intestinal tract. It is also parasitostatic and in some cases produces side-effects. Therefore, an alternative to the treatment of this severe human disease is necessary. In this context, the repositioning of drugs combined with nanotechnology to improve the bioavailability of drugs emerges as a useful, fast and inexpensive tool for the treatment of neglected diseases. The in vitro and in vivo efficacy of dichlorophen (DCP), an antiparasitic agent for intestinal parasites, and silica nanoparticles modified with DCP (NP-DCP) was evaluated against E. multilocularis larval stage. Both formulations showed a time and dose-dependent in vitro effect against protoscoleces. The NP-DCP had a greater in vitro efficacy than the drug alone or ABZ. In vivo studies demonstrated that the NP-DCP (4 mg kg−1) had similar efficacy to ABZ (25 mg kg−1) and greater activity than the free DCP. Therefore, the repurposing of DCP combined with silica nanoparticles could be an alternative for the treatment of echinococcosis.

Keywords

Albendazolealveolar echinococcosisdichlorophenEchinococcus multilocularissilica nanoparticles
Type
Research Article
Information
Parasitology , Volume 146 , Issue 13 , November 2019 , pp. 1620 - 1630
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Copyright
Copyright © Cambridge University Press 2019 

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