Benznidazole/Poloxamer 407 Solid Dispersion as a New Strategy to Improve the Treatment of Experimental Trypanosoma cruzi Infection
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 solubilit...
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| Formato: | Artículo |
| Lenguaje: | Inglés |
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American Society of Parasitologists
2024
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| Acceso en línea: | http://hdl.handle.net/20.500.12123/16803 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 |
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| author | Devies, Carolina Simonazzi, Analía Micheloud, Juan Francisco Ragone, Paula Gabriela Cid, Alicia Graciela Sánchez Negrette, Olga Bermúdez, José María Parada, Luis Antonio |
| author_browse | Bermúdez, José María Cid, Alicia Graciela Devies, Carolina Micheloud, Juan Francisco Parada, Luis Antonio Ragone, Paula Gabriela Simonazzi, Analía Sánchez Negrette, Olga |
| author_facet | Devies, Carolina Simonazzi, Analía Micheloud, Juan Francisco Ragone, Paula Gabriela Cid, Alicia Graciela Sánchez Negrette, Olga Bermúdez, José María Parada, Luis Antonio |
| author_sort | Devies, Carolina |
| collection | INTA Digital |
| 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. |
| format | Artículo |
| id | INTA16803 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2024 |
| publishDateRange | 2024 |
| publishDateSort | 2024 |
| publisher | American Society of Parasitologists |
| publisherStr | American Society of Parasitologists |
| record_format | dspace |
| spelling | INTA168032025-07-24T11:38:47Z Benznidazole/Poloxamer 407 Solid Dispersion as a New Strategy to Improve the Treatment of Experimental Trypanosoma cruzi Infection Devies, Carolina Simonazzi, Analía Micheloud, Juan Francisco Ragone, Paula Gabriela Cid, Alicia Graciela Sánchez Negrette, Olga Bermúdez, José María Parada, Luis Antonio Dispersión Improve Treatment Trypanosoma cruzi Enfermedad de Chagas Terapia Chagas Disease Therapy Benznidazole Tratamiento de las Enfermedades Nifurtimox Disease Treatment 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. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental; Argentina. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina Fil: Simonazzi, Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Investigaciones para la Industria Química; Argentina. Universidad Nacional de Salta. Facultad de Ingeniería. Instituto de Investigaciones para la Industria Química; Argentina Fil: Micheloud, Juan Francisco. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Investigación Animal del Chaco Semiárido, Área de Investigación en Salud Animal; Argentina Fil: Ragone, Paula Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental; Argentina. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina Fil: Cid, Alicia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Investigaciones para la Industria Química; Argentina. Universidad Nacional de Salta. Facultad de Ingeniería. 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: Bermudez, Jose Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Investigaciones para la Industria Química; Argentina. Universidad Nacional de Salta. Facultad de Ingeniería. Instituto de Investigaciones para la Industria Química; Argentina Fil: Parada, Luis Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental; Argentina. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina 2024-02-26T14:59:44Z 2024-02-26T14:59:44Z 2020-05-04 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/16803 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 https://doi.org/10.1645/19-80 eng info:eu-repo/semantics/restrictedAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf American Society of Parasitologists Journal of Parasitology 106 (3) : 323-333 (2020) |
| spellingShingle | Dispersión Improve Treatment Trypanosoma cruzi Enfermedad de Chagas Terapia Chagas Disease Therapy Benznidazole Tratamiento de las Enfermedades Nifurtimox Disease Treatment Devies, Carolina Simonazzi, Analía Micheloud, Juan Francisco Ragone, Paula Gabriela Cid, Alicia Graciela Sánchez Negrette, Olga Bermúdez, José María Parada, Luis Antonio 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 |
| 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_short | 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 |
| topic | Dispersión Improve Treatment Trypanosoma cruzi Enfermedad de Chagas Terapia Chagas Disease Therapy Benznidazole Tratamiento de las Enfermedades Nifurtimox Disease Treatment |
| url | http://hdl.handle.net/20.500.12123/16803 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 |
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