Benznidazole/Poloxamer 407 Solid Dispersion as a New Strategy to Improve the Treatment of Experimental Trypanosoma cruzi Infection

Autores
Davies, Carolina; Simonazzi, Analía; Micheloud, Juan Francisco; Ragone, Paula Gabriela; Cid, Alicia Graciela; Sánchez Negrette, Olga; Bermúdez, José María; Parada, Luis Antonio
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Benznidazole and nifurtimox are the only drugs specifically approved for the treatment of Chagas disease. Both compounds are given orally in tablets, but occasionally are ineffective and cause adverse effects. Benznidazole, the first-line treatment in many countries, is a compound with low solubility in water that is administered at high doses for long periods of time. To improve its solubility, we developed a new liquid formulation on the basis of solid dispersions (SD) using the amphiphilic polymer poloxamer 407. Herein we present data on its trypanocidal performance in mouse models of acute and chronic Trypanosoma cruzi infection. SD at doses of 60 or 15 mg/kg per day given with different administration schedules were compared with the commercial formulation (CF; 50 mg/kg per day) and vehicle. The SD performance was assessed by direct parasitemia, total anti-T. cruzi antibodies, and parasitic burden in tissues after 4 or 6 mo posttreatment. The efficacy of the SD was equivalent to the CF but without manifest side effects and hepatotoxicity. Considering our previous data on solubility, together with these on efficacy, this new liquid formulation represents a promising alternative for the treatment of Chagas disease, particularly in cases when dosing poses a challenge, as in infants.
Estación Experimental Agropecuaria Salta
Fil: Davies, Carolina. Universidad Nacional de Salta. Instituto de Patología Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Simonazzi, Analía. Universidad Nacional de Salta. Instituto de Investigaciones para la Industria Química; Argentina
Fil: Micheloud, Juan Francisco. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta. Grupo de trabajo de Patología. Epidemiologia e investigación Diagnostica, Área de Sanidad ANIMAL-IIACS LEALES/INTA Salta; Argentina.
Fil: Ragone, Paula Gabriela. Universidad Católica de Salta. Facultad de Ciencias Agrarias y Veterinarias. Cátedra de inmunología; Argentina.
Fil:Cid, Alicia Graciela. Universidad Nacional de Salta. Instituto de investigaciones para la Industria Química; Argentina.
Fil: Sánchez Negrette, Olga. Universidad Católica de Salta. Facultad de Ciencias Agrarias y Veterinarias. Cátedra de inmunología; Argentina
Fil: Bermúdez, José María. Universidad Nacional de Salta. Instituto de Investigación para la industria Química; Argentina.
Fil: Parada, Luis Antonio. Universidad Nacional de Salta. Instituto de Patología Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fuente
Journal of Parasitology 106 (3) : 323-333 (May 2020)
Materia
Trypanosoma
Trypanosoma cruzi
Control de Enfermedades
Diseases Control
Benznidazole
Poloxamer
Nivel de accesibilidad
acceso restringido
Condiciones de uso
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
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oai_identifier_str oai:localhost:20.500.12123/9817
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spelling Benznidazole/Poloxamer 407 Solid Dispersion as a New Strategy to Improve the Treatment of Experimental Trypanosoma cruzi InfectionDavies, CarolinaSimonazzi, AnalíaMicheloud, Juan FranciscoRagone, Paula GabrielaCid, Alicia GracielaSánchez Negrette, OlgaBermúdez, José MaríaParada, Luis AntonioTrypanosomaTrypanosoma cruziControl de EnfermedadesDiseases ControlBenznidazolePoloxamerBenznidazole and nifurtimox are the only drugs specifically approved for the treatment of Chagas disease. Both compounds are given orally in tablets, but occasionally are ineffective and cause adverse effects. Benznidazole, the first-line treatment in many countries, is a compound with low solubility in water that is administered at high doses for long periods of time. To improve its solubility, we developed a new liquid formulation on the basis of solid dispersions (SD) using the amphiphilic polymer poloxamer 407. Herein we present data on its trypanocidal performance in mouse models of acute and chronic Trypanosoma cruzi infection. SD at doses of 60 or 15 mg/kg per day given with different administration schedules were compared with the commercial formulation (CF; 50 mg/kg per day) and vehicle. The SD performance was assessed by direct parasitemia, total anti-T. cruzi antibodies, and parasitic burden in tissues after 4 or 6 mo posttreatment. The efficacy of the SD was equivalent to the CF but without manifest side effects and hepatotoxicity. Considering our previous data on solubility, together with these on efficacy, this new liquid formulation represents a promising alternative for the treatment of Chagas disease, particularly in cases when dosing poses a challenge, as in infants.Estación Experimental Agropecuaria SaltaFil: Davies, Carolina. Universidad Nacional de Salta. Instituto de Patología Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Simonazzi, Analía. Universidad Nacional de Salta. Instituto de Investigaciones para la Industria Química; ArgentinaFil: Micheloud, Juan Francisco. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta. Grupo de trabajo de Patología. Epidemiologia e investigación Diagnostica, Área de Sanidad ANIMAL-IIACS LEALES/INTA Salta; Argentina.Fil: Ragone, Paula Gabriela. Universidad Católica de Salta. Facultad de Ciencias Agrarias y Veterinarias. Cátedra de inmunología; Argentina.Fil:Cid, Alicia Graciela. Universidad Nacional de Salta. Instituto de investigaciones para la Industria Química; Argentina.Fil: Sánchez Negrette, Olga. Universidad Católica de Salta. Facultad de Ciencias Agrarias y Veterinarias. Cátedra de inmunología; ArgentinaFil: Bermúdez, José María. Universidad Nacional de Salta. Instituto de Investigación para la industria Química; Argentina.Fil: Parada, Luis Antonio. Universidad Nacional de Salta. Instituto de Patología Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAmerican Society of Parasitologists2021-07-15T12:02:47Z2021-07-15T12:02:47Z2020-05-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/9817https://bioone.org/journals/journal-of-parasitology/volume-106/issue-3/19-80/Benznidazole-Poloxamer-407-Solid-Dispersion-as-a-New-Strategy-to/10.1645/19-80.short0022-33951937-2345https://doi.org/10.1645/19-80Journal of Parasitology 106 (3) : 323-333 (May 2020)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/restrictedAccess2025-09-18T10:08:16Zoai:localhost:20.500.12123/9817instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-09-18 10:08:17.299INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Benznidazole/Poloxamer 407 Solid Dispersion as a New Strategy to Improve the Treatment of Experimental Trypanosoma cruzi Infection
title Benznidazole/Poloxamer 407 Solid Dispersion as a New Strategy to Improve the Treatment of Experimental Trypanosoma cruzi Infection
spellingShingle Benznidazole/Poloxamer 407 Solid Dispersion as a New Strategy to Improve the Treatment of Experimental Trypanosoma cruzi Infection
Davies, Carolina
Trypanosoma
Trypanosoma cruzi
Control de Enfermedades
Diseases Control
Benznidazole
Poloxamer
title_short Benznidazole/Poloxamer 407 Solid Dispersion as a New Strategy to Improve the Treatment of Experimental Trypanosoma cruzi Infection
title_full Benznidazole/Poloxamer 407 Solid Dispersion as a New Strategy to Improve the Treatment of Experimental Trypanosoma cruzi Infection
title_fullStr Benznidazole/Poloxamer 407 Solid Dispersion as a New Strategy to Improve the Treatment of Experimental Trypanosoma cruzi Infection
title_full_unstemmed Benznidazole/Poloxamer 407 Solid Dispersion as a New Strategy to Improve the Treatment of Experimental Trypanosoma cruzi Infection
title_sort Benznidazole/Poloxamer 407 Solid Dispersion as a New Strategy to Improve the Treatment of Experimental Trypanosoma cruzi Infection
dc.creator.none.fl_str_mv Davies, Carolina
Simonazzi, Analía
Micheloud, Juan Francisco
Ragone, Paula Gabriela
Cid, Alicia Graciela
Sánchez Negrette, Olga
Bermúdez, José María
Parada, Luis Antonio
author Davies, Carolina
author_facet Davies, Carolina
Simonazzi, Analía
Micheloud, Juan Francisco
Ragone, Paula Gabriela
Cid, Alicia Graciela
Sánchez Negrette, Olga
Bermúdez, José María
Parada, Luis Antonio
author_role author
author2 Simonazzi, Analía
Micheloud, Juan Francisco
Ragone, Paula Gabriela
Cid, Alicia Graciela
Sánchez Negrette, Olga
Bermúdez, José María
Parada, Luis Antonio
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Trypanosoma
Trypanosoma cruzi
Control de Enfermedades
Diseases Control
Benznidazole
Poloxamer
topic Trypanosoma
Trypanosoma cruzi
Control de Enfermedades
Diseases Control
Benznidazole
Poloxamer
dc.description.none.fl_txt_mv Benznidazole and nifurtimox are the only drugs specifically approved for the treatment of Chagas disease. Both compounds are given orally in tablets, but occasionally are ineffective and cause adverse effects. Benznidazole, the first-line treatment in many countries, is a compound with low solubility in water that is administered at high doses for long periods of time. To improve its solubility, we developed a new liquid formulation on the basis of solid dispersions (SD) using the amphiphilic polymer poloxamer 407. Herein we present data on its trypanocidal performance in mouse models of acute and chronic Trypanosoma cruzi infection. SD at doses of 60 or 15 mg/kg per day given with different administration schedules were compared with the commercial formulation (CF; 50 mg/kg per day) and vehicle. The SD performance was assessed by direct parasitemia, total anti-T. cruzi antibodies, and parasitic burden in tissues after 4 or 6 mo posttreatment. The efficacy of the SD was equivalent to the CF but without manifest side effects and hepatotoxicity. Considering our previous data on solubility, together with these on efficacy, this new liquid formulation represents a promising alternative for the treatment of Chagas disease, particularly in cases when dosing poses a challenge, as in infants.
Estación Experimental Agropecuaria Salta
Fil: Davies, Carolina. Universidad Nacional de Salta. Instituto de Patología Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Simonazzi, Analía. Universidad Nacional de Salta. Instituto de Investigaciones para la Industria Química; Argentina
Fil: Micheloud, Juan Francisco. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta. Grupo de trabajo de Patología. Epidemiologia e investigación Diagnostica, Área de Sanidad ANIMAL-IIACS LEALES/INTA Salta; Argentina.
Fil: Ragone, Paula Gabriela. Universidad Católica de Salta. Facultad de Ciencias Agrarias y Veterinarias. Cátedra de inmunología; Argentina.
Fil:Cid, Alicia Graciela. Universidad Nacional de Salta. Instituto de investigaciones para la Industria Química; Argentina.
Fil: Sánchez Negrette, Olga. Universidad Católica de Salta. Facultad de Ciencias Agrarias y Veterinarias. Cátedra de inmunología; Argentina
Fil: Bermúdez, José María. Universidad Nacional de Salta. Instituto de Investigación para la industria Química; Argentina.
Fil: Parada, Luis Antonio. Universidad Nacional de Salta. Instituto de Patología Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Benznidazole and nifurtimox are the only drugs specifically approved for the treatment of Chagas disease. Both compounds are given orally in tablets, but occasionally are ineffective and cause adverse effects. Benznidazole, the first-line treatment in many countries, is a compound with low solubility in water that is administered at high doses for long periods of time. To improve its solubility, we developed a new liquid formulation on the basis of solid dispersions (SD) using the amphiphilic polymer poloxamer 407. Herein we present data on its trypanocidal performance in mouse models of acute and chronic Trypanosoma cruzi infection. SD at doses of 60 or 15 mg/kg per day given with different administration schedules were compared with the commercial formulation (CF; 50 mg/kg per day) and vehicle. The SD performance was assessed by direct parasitemia, total anti-T. cruzi antibodies, and parasitic burden in tissues after 4 or 6 mo posttreatment. The efficacy of the SD was equivalent to the CF but without manifest side effects and hepatotoxicity. Considering our previous data on solubility, together with these on efficacy, this new liquid formulation represents a promising alternative for the treatment of Chagas disease, particularly in cases when dosing poses a challenge, as in infants.
publishDate 2020
dc.date.none.fl_str_mv 2020-05-04
2021-07-15T12:02:47Z
2021-07-15T12:02:47Z
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12123/9817
https://bioone.org/journals/journal-of-parasitology/volume-106/issue-3/19-80/Benznidazole-Poloxamer-407-Solid-Dispersion-as-a-New-Strategy-to/10.1645/19-80.short
0022-3395
1937-2345
https://doi.org/10.1645/19-80
url http://hdl.handle.net/20.500.12123/9817
https://bioone.org/journals/journal-of-parasitology/volume-106/issue-3/19-80/Benznidazole-Poloxamer-407-Solid-Dispersion-as-a-New-Strategy-to/10.1645/19-80.short
https://doi.org/10.1645/19-80
identifier_str_mv 0022-3395
1937-2345
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/restrictedAccess
eu_rights_str_mv restrictedAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society of Parasitologists
publisher.none.fl_str_mv American Society of Parasitologists
dc.source.none.fl_str_mv Journal of Parasitology 106 (3) : 323-333 (May 2020)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
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score 13.000565

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