3D-Printed Tablets of Nifurtimox: In Vitro and In Vivo Anti-Trypanosoma cruzi Studies

Autores
Bedogni, Giselle Rocio; Lima, Ana Luiza; Gross, Idejan P.; Menezes, Tatiana Prata; Talvani, Andre; Cunha-Filho, Marcilio; Salomon, Claudio Javier
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chagas disease is a neglected tropical disease causedby infection with the parasite Trypanosoma cruzi. Benznidazole and nifurtimox are theonly approved drugs for treating this condition, but their low aqueous solubility maylead to erratic bioavailability. This work aimed for the first time to formulate tabletsof nifurtimox by hot melt extrusion coupled with 3D printing as a strategy to increasedrug dissolution and the production of tablets with dosage on demand. Methods: Differentpharmaceutical-grade polymers were evaluated through film casting, and those withpromising nifurtimox amorphization capacity were further used to prepare filaments by hotmelt extrusion. The printability of the obtained filaments was tested, and the polyvinyl alcoholfilament was further used for printing tablets containing 120 and 60 mg of nifurtimox.Results: Three-dimensional tablets showed a remarkable improvement in the drug dissolutionrate compared to commercial tablets and a dissolution efficiency 2.8 times higher.In vivo studies were carried out on Swiss mice. Parasitemia curves of nifurtimox printedtablets were significantly superior to the pure drug. Moreover, NFX 3D tablets provided asimilar Trypanosoma cruzi reduction in plasmatic concentration to benznidazole, the goldstandarddrug for acute-phase treatment of the Chagas disease. Conclusions: The findingsof this work showed that hot melt extrusion coupled with 3D printing is a promising alternativefor increasing nifurtimox biopharmaceutical properties and an attractive approachfor personalized medicine.
Fil: Bedogni, Giselle Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Fil: Lima, Ana Luiza. Universidade do Brasília; Brasil
Fil: Gross, Idejan P.. Universidade do Brasília; Brasil
Fil: Menezes, Tatiana Prata. Universidad Federal de Ouro Preto; Brasil
Fil: Talvani, Andre. Universidad Federal de Ouro Preto; Brasil
Fil: Cunha-Filho, Marcilio. Universidade do Brasília; Brasil
Fil: Salomon, Claudio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Materia
Nifurtimox
Film casting
Hot melt extrusion
3D printing
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/285379
Acceder
id CONICETDig_e0cbdab0577a871334fa0bc6fc28f9a2
oai_identifier_str oai:ri.conicet.gov.ar:11336/285379
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 3D-Printed Tablets of Nifurtimox: In Vitro and In Vivo Anti-Trypanosoma cruzi StudiesBedogni, Giselle RocioLima, Ana LuizaGross, Idejan P.Menezes, Tatiana PrataTalvani, AndreCunha-Filho, MarcilioSalomon, Claudio JavierNifurtimoxFilm castingHot melt extrusion3D printinghttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Chagas disease is a neglected tropical disease causedby infection with the parasite Trypanosoma cruzi. Benznidazole and nifurtimox are theonly approved drugs for treating this condition, but their low aqueous solubility maylead to erratic bioavailability. This work aimed for the first time to formulate tabletsof nifurtimox by hot melt extrusion coupled with 3D printing as a strategy to increasedrug dissolution and the production of tablets with dosage on demand. Methods: Differentpharmaceutical-grade polymers were evaluated through film casting, and those withpromising nifurtimox amorphization capacity were further used to prepare filaments by hotmelt extrusion. The printability of the obtained filaments was tested, and the polyvinyl alcoholfilament was further used for printing tablets containing 120 and 60 mg of nifurtimox.Results: Three-dimensional tablets showed a remarkable improvement in the drug dissolutionrate compared to commercial tablets and a dissolution efficiency 2.8 times higher.In vivo studies were carried out on Swiss mice. Parasitemia curves of nifurtimox printedtablets were significantly superior to the pure drug. Moreover, NFX 3D tablets provided asimilar Trypanosoma cruzi reduction in plasmatic concentration to benznidazole, the goldstandarddrug for acute-phase treatment of the Chagas disease. Conclusions: The findingsof this work showed that hot melt extrusion coupled with 3D printing is a promising alternativefor increasing nifurtimox biopharmaceutical properties and an attractive approachfor personalized medicine.Fil: Bedogni, Giselle Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Lima, Ana Luiza. Universidade do Brasília; BrasilFil: Gross, Idejan P.. Universidade do Brasília; BrasilFil: Menezes, Tatiana Prata. Universidad Federal de Ouro Preto; BrasilFil: Talvani, Andre. Universidad Federal de Ouro Preto; BrasilFil: Cunha-Filho, Marcilio. Universidade do Brasília; BrasilFil: Salomon, Claudio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaMDPI2025-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/285379Bedogni, Giselle Rocio; Lima, Ana Luiza; Gross, Idejan P.; Menezes, Tatiana Prata; Talvani, Andre; et al.; 3D-Printed Tablets of Nifurtimox: In Vitro and In Vivo Anti-Trypanosoma cruzi Studies; MDPI; Pharmaceutics; 17; 1; 1-2025; 1-161999-4923CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1999-4923/17/1/80info:eu-repo/semantics/altIdentifier/doi/10.3390/pharmaceutics17010080info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T14:36:23Zoai:ri.conicet.gov.ar:11336/285379instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-08-25 14:36:23.898CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv 3D-Printed Tablets of Nifurtimox: In Vitro and In Vivo Anti-Trypanosoma cruzi Studies
title 3D-Printed Tablets of Nifurtimox: In Vitro and In Vivo Anti-Trypanosoma cruzi Studies
spellingShingle 3D-Printed Tablets of Nifurtimox: In Vitro and In Vivo Anti-Trypanosoma cruzi Studies
Bedogni, Giselle Rocio
Nifurtimox
Film casting
Hot melt extrusion
3D printing
title_short 3D-Printed Tablets of Nifurtimox: In Vitro and In Vivo Anti-Trypanosoma cruzi Studies
title_full 3D-Printed Tablets of Nifurtimox: In Vitro and In Vivo Anti-Trypanosoma cruzi Studies
title_fullStr 3D-Printed Tablets of Nifurtimox: In Vitro and In Vivo Anti-Trypanosoma cruzi Studies
title_full_unstemmed 3D-Printed Tablets of Nifurtimox: In Vitro and In Vivo Anti-Trypanosoma cruzi Studies
title_sort 3D-Printed Tablets of Nifurtimox: In Vitro and In Vivo Anti-Trypanosoma cruzi Studies
dc.creator.none.fl_str_mv Bedogni, Giselle Rocio
Lima, Ana Luiza
Gross, Idejan P.
Menezes, Tatiana Prata
Talvani, Andre
Cunha-Filho, Marcilio
Salomon, Claudio Javier
author Bedogni, Giselle Rocio
author_facet Bedogni, Giselle Rocio
Lima, Ana Luiza
Gross, Idejan P.
Menezes, Tatiana Prata
Talvani, Andre
Cunha-Filho, Marcilio
Salomon, Claudio Javier
author_role author
author2 Lima, Ana Luiza
Gross, Idejan P.
Menezes, Tatiana Prata
Talvani, Andre
Cunha-Filho, Marcilio
Salomon, Claudio Javier
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Nifurtimox
Film casting
Hot melt extrusion
3D printing
topic Nifurtimox
Film casting
Hot melt extrusion
3D printing
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Chagas disease is a neglected tropical disease causedby infection with the parasite Trypanosoma cruzi. Benznidazole and nifurtimox are theonly approved drugs for treating this condition, but their low aqueous solubility maylead to erratic bioavailability. This work aimed for the first time to formulate tabletsof nifurtimox by hot melt extrusion coupled with 3D printing as a strategy to increasedrug dissolution and the production of tablets with dosage on demand. Methods: Differentpharmaceutical-grade polymers were evaluated through film casting, and those withpromising nifurtimox amorphization capacity were further used to prepare filaments by hotmelt extrusion. The printability of the obtained filaments was tested, and the polyvinyl alcoholfilament was further used for printing tablets containing 120 and 60 mg of nifurtimox.Results: Three-dimensional tablets showed a remarkable improvement in the drug dissolutionrate compared to commercial tablets and a dissolution efficiency 2.8 times higher.In vivo studies were carried out on Swiss mice. Parasitemia curves of nifurtimox printedtablets were significantly superior to the pure drug. Moreover, NFX 3D tablets provided asimilar Trypanosoma cruzi reduction in plasmatic concentration to benznidazole, the goldstandarddrug for acute-phase treatment of the Chagas disease. Conclusions: The findingsof this work showed that hot melt extrusion coupled with 3D printing is a promising alternativefor increasing nifurtimox biopharmaceutical properties and an attractive approachfor personalized medicine.
Fil: Bedogni, Giselle Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Fil: Lima, Ana Luiza. Universidade do Brasília; Brasil
Fil: Gross, Idejan P.. Universidade do Brasília; Brasil
Fil: Menezes, Tatiana Prata. Universidad Federal de Ouro Preto; Brasil
Fil: Talvani, Andre. Universidad Federal de Ouro Preto; Brasil
Fil: Cunha-Filho, Marcilio. Universidade do Brasília; Brasil
Fil: Salomon, Claudio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
description Chagas disease is a neglected tropical disease causedby infection with the parasite Trypanosoma cruzi. Benznidazole and nifurtimox are theonly approved drugs for treating this condition, but their low aqueous solubility maylead to erratic bioavailability. This work aimed for the first time to formulate tabletsof nifurtimox by hot melt extrusion coupled with 3D printing as a strategy to increasedrug dissolution and the production of tablets with dosage on demand. Methods: Differentpharmaceutical-grade polymers were evaluated through film casting, and those withpromising nifurtimox amorphization capacity were further used to prepare filaments by hotmelt extrusion. The printability of the obtained filaments was tested, and the polyvinyl alcoholfilament was further used for printing tablets containing 120 and 60 mg of nifurtimox.Results: Three-dimensional tablets showed a remarkable improvement in the drug dissolutionrate compared to commercial tablets and a dissolution efficiency 2.8 times higher.In vivo studies were carried out on Swiss mice. Parasitemia curves of nifurtimox printedtablets were significantly superior to the pure drug. Moreover, NFX 3D tablets provided asimilar Trypanosoma cruzi reduction in plasmatic concentration to benznidazole, the goldstandarddrug for acute-phase treatment of the Chagas disease. Conclusions: The findingsof this work showed that hot melt extrusion coupled with 3D printing is a promising alternativefor increasing nifurtimox biopharmaceutical properties and an attractive approachfor personalized medicine.
publishDate 2025
dc.date.none.fl_str_mv 2025-01
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/11336/285379
Bedogni, Giselle Rocio; Lima, Ana Luiza; Gross, Idejan P.; Menezes, Tatiana Prata; Talvani, Andre; et al.; 3D-Printed Tablets of Nifurtimox: In Vitro and In Vivo Anti-Trypanosoma cruzi Studies; MDPI; Pharmaceutics; 17; 1; 1-2025; 1-16
1999-4923
CONICET Digital
CONICET
url http://hdl.handle.net/11336/285379
identifier_str_mv Bedogni, Giselle Rocio; Lima, Ana Luiza; Gross, Idejan P.; Menezes, Tatiana Prata; Talvani, Andre; et al.; 3D-Printed Tablets of Nifurtimox: In Vitro and In Vivo Anti-Trypanosoma cruzi Studies; MDPI; Pharmaceutics; 17; 1; 1-2025; 1-16
1999-4923
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1999-4923/17/1/80
info:eu-repo/semantics/altIdentifier/doi/10.3390/pharmaceutics17010080
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.24418

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