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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| Format: | Artículo |
| Language: | Inglés |
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American Society of Parasitologists
2021
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| Online Access: | 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 |
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| author | Davies, 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 Davies, Carolina Micheloud, Juan Francisco Parada, Luis Antonio Ragone, Paula Gabriela Simonazzi, Analía Sánchez Negrette, Olga |
| 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_sort | Davies, 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 | INTA9817 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2021 |
| publishDateRange | 2021 |
| publishDateSort | 2021 |
| publisher | American Society of Parasitologists |
| publisherStr | American Society of Parasitologists |
| record_format | dspace |
| spelling | INTA98172021-07-15T12:30:21Z Benznidazole/Poloxamer 407 Solid Dispersion as a New Strategy to Improve the Treatment of Experimental Trypanosoma cruzi Infection Davies, Carolina Simonazzi, Analía Micheloud, Juan Francisco Ragone, Paula Gabriela Cid, Alicia Graciela Sánchez Negrette, Olga Bermúdez, José María Parada, Luis Antonio Trypanosoma Trypanosoma cruzi Control de Enfermedades Diseases Control Benznidazole Poloxamer 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 2021-07-15T12:02:47Z 2021-07-15T12:02:47Z 2020-05-04 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/9817 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 eng info:eu-repo/semantics/restrictedAccess application/pdf American Society of Parasitologists Journal of Parasitology 106 (3) : 323-333 (May 2020) |
| spellingShingle | Trypanosoma Trypanosoma cruzi Control de Enfermedades Diseases Control Benznidazole Poloxamer Davies, 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 | Trypanosoma Trypanosoma cruzi Control de Enfermedades Diseases Control Benznidazole Poloxamer |
| 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 |
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