Multi-kinetic release of benznidazole-loaded multiparticulate drug delivery systems based on polymethacrylate interpolyelectrolyte complexes

Autores
García, Mónica Cristina; Martinelli, Marisa; Ponce, Nicolás Eric; Sanmarco, Liliana Maria; Aoki, Maria del Pilar; Manzo, Ruben Hilario; Jimenez Kairuz, Alvaro Federico
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Interpolyelectrolyte complexes (IPEC) formulated as multiparticulate drug delivery systems (MDDS) are interesting carriers to improve drug’ performance. Benznidazole (BZ) is the first–line drug for Chagas treatment; however, it presents side effects and toxicity, conditioning its efficacy and safety. The goal of this work was to obtain novel MDDS composed by IPEC based on different polymethacrylate carriers loaded with BZ and to investigate in vitro drug delivery performance for oral administration. Physicochemical characterizations were studied and preclinical studies in a murine model of acute Chagas disease were also performed. The MDDS composed by BZ-loaded IPEC based on polymethacrylates were obtained by casting solvent followed by wet granulation methods with yields >83%. FT-IR demonstrated ionic interaction between the polyelectrolytes. Confocal microscopy, DSC and PXRD revealed a fraction uniformly distributed of free BZ on the multiparticles. The rheological evaluation of the MDDS showed adequate flow features for their formulation in hard gelatin-capsules. The type and composition of IPEC conditioned the modulation of BZ release and fluid uptake results. MDDS based on more hydrophylic Eudragit® showed very fast dissolution (Q15min > 85%), while an extended release (Q120min ≤ 40%) for the hydrophobic ones was observed. Capsules containing a combination of two MDDS with different release profile of BZ showed promising properties to improve Chagas disease pharmacotherapy in the preliminary in vivo assay performed, in which the BZ-loaded MDDS exhibited efficacy to reduce parasitemia, while decreasing the levels of liver injury markers in comparison to BZ conventional treatment. Multi-kinetic BZ delivery systems developed are interesting pharmaceutical alternatives to improve the treatment of Chagas disease.
Fil: García, Mónica Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Martinelli, Marisa. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada (IPQA), CONICET and Laboratorio de Materiales Poliméricos (LAMAP), Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina; Argentina
Fil: Ponce, Nicolás Eric. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Sanmarco, Liliana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Aoki, Maria del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Manzo, Ruben Hilario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Jimenez Kairuz, Alvaro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Materia
BENZNIDAZOLE
CHAGAS DISEASE
EUDRAGIT®
MULTIPARTICULATE DRUG DELIVERY SYSTEMS
POLYELECTROLYTE COMPLEXES
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/92600
Acceder
id CONICETDig_d50152d9dc1c06f45135c6f66de02db6
oai_identifier_str oai:ri.conicet.gov.ar:11336/92600
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Multi-kinetic release of benznidazole-loaded multiparticulate drug delivery systems based on polymethacrylate interpolyelectrolyte complexesGarcía, Mónica CristinaMartinelli, MarisaPonce, Nicolás EricSanmarco, Liliana MariaAoki, Maria del PilarManzo, Ruben HilarioJimenez Kairuz, Alvaro FedericoBENZNIDAZOLECHAGAS DISEASEEUDRAGIT®MULTIPARTICULATE DRUG DELIVERY SYSTEMSPOLYELECTROLYTE COMPLEXEShttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Interpolyelectrolyte complexes (IPEC) formulated as multiparticulate drug delivery systems (MDDS) are interesting carriers to improve drug’ performance. Benznidazole (BZ) is the first–line drug for Chagas treatment; however, it presents side effects and toxicity, conditioning its efficacy and safety. The goal of this work was to obtain novel MDDS composed by IPEC based on different polymethacrylate carriers loaded with BZ and to investigate in vitro drug delivery performance for oral administration. Physicochemical characterizations were studied and preclinical studies in a murine model of acute Chagas disease were also performed. The MDDS composed by BZ-loaded IPEC based on polymethacrylates were obtained by casting solvent followed by wet granulation methods with yields >83%. FT-IR demonstrated ionic interaction between the polyelectrolytes. Confocal microscopy, DSC and PXRD revealed a fraction uniformly distributed of free BZ on the multiparticles. The rheological evaluation of the MDDS showed adequate flow features for their formulation in hard gelatin-capsules. The type and composition of IPEC conditioned the modulation of BZ release and fluid uptake results. MDDS based on more hydrophylic Eudragit® showed very fast dissolution (Q15min > 85%), while an extended release (Q120min ≤ 40%) for the hydrophobic ones was observed. Capsules containing a combination of two MDDS with different release profile of BZ showed promising properties to improve Chagas disease pharmacotherapy in the preliminary in vivo assay performed, in which the BZ-loaded MDDS exhibited efficacy to reduce parasitemia, while decreasing the levels of liver injury markers in comparison to BZ conventional treatment. Multi-kinetic BZ delivery systems developed are interesting pharmaceutical alternatives to improve the treatment of Chagas disease.Fil: García, Mónica Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Martinelli, Marisa. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada (IPQA), CONICET and Laboratorio de Materiales Poliméricos (LAMAP), Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina; ArgentinaFil: Ponce, Nicolás Eric. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Sanmarco, Liliana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Aoki, Maria del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Manzo, Ruben Hilario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Jimenez Kairuz, Alvaro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaElsevier Science2018-07-23info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/92600García, Mónica Cristina; Martinelli, Marisa; Ponce, Nicolás Eric; Sanmarco, Liliana Maria; Aoki, Maria del Pilar; et al.; Multi-kinetic release of benznidazole-loaded multiparticulate drug delivery systems based on polymethacrylate interpolyelectrolyte complexes; Elsevier Science; European Journal Of Pharmaceutical Sciences; 120; 23-7-2018; 107-1220928-0987CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0928098718301994?via%3Dihubinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejps.2018.04.034info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:34:19Zoai:ri.conicet.gov.ar:11336/92600instacron: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:34982025-10-22 11:34:20.253CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Multi-kinetic release of benznidazole-loaded multiparticulate drug delivery systems based on polymethacrylate interpolyelectrolyte complexes
title Multi-kinetic release of benznidazole-loaded multiparticulate drug delivery systems based on polymethacrylate interpolyelectrolyte complexes
spellingShingle Multi-kinetic release of benznidazole-loaded multiparticulate drug delivery systems based on polymethacrylate interpolyelectrolyte complexes
García, Mónica Cristina
BENZNIDAZOLE
CHAGAS DISEASE
EUDRAGIT®
MULTIPARTICULATE DRUG DELIVERY SYSTEMS
POLYELECTROLYTE COMPLEXES
title_short Multi-kinetic release of benznidazole-loaded multiparticulate drug delivery systems based on polymethacrylate interpolyelectrolyte complexes
title_full Multi-kinetic release of benznidazole-loaded multiparticulate drug delivery systems based on polymethacrylate interpolyelectrolyte complexes
title_fullStr Multi-kinetic release of benznidazole-loaded multiparticulate drug delivery systems based on polymethacrylate interpolyelectrolyte complexes
title_full_unstemmed Multi-kinetic release of benznidazole-loaded multiparticulate drug delivery systems based on polymethacrylate interpolyelectrolyte complexes
title_sort Multi-kinetic release of benznidazole-loaded multiparticulate drug delivery systems based on polymethacrylate interpolyelectrolyte complexes
dc.creator.none.fl_str_mv García, Mónica Cristina
Martinelli, Marisa
Ponce, Nicolás Eric
Sanmarco, Liliana Maria
Aoki, Maria del Pilar
Manzo, Ruben Hilario
Jimenez Kairuz, Alvaro Federico
author García, Mónica Cristina
author_facet García, Mónica Cristina
Martinelli, Marisa
Ponce, Nicolás Eric
Sanmarco, Liliana Maria
Aoki, Maria del Pilar
Manzo, Ruben Hilario
Jimenez Kairuz, Alvaro Federico
author_role author
author2 Martinelli, Marisa
Ponce, Nicolás Eric
Sanmarco, Liliana Maria
Aoki, Maria del Pilar
Manzo, Ruben Hilario
Jimenez Kairuz, Alvaro Federico
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv BENZNIDAZOLE
CHAGAS DISEASE
EUDRAGIT®
MULTIPARTICULATE DRUG DELIVERY SYSTEMS
POLYELECTROLYTE COMPLEXES
topic BENZNIDAZOLE
CHAGAS DISEASE
EUDRAGIT®
MULTIPARTICULATE DRUG DELIVERY SYSTEMS
POLYELECTROLYTE COMPLEXES
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Interpolyelectrolyte complexes (IPEC) formulated as multiparticulate drug delivery systems (MDDS) are interesting carriers to improve drug’ performance. Benznidazole (BZ) is the first–line drug for Chagas treatment; however, it presents side effects and toxicity, conditioning its efficacy and safety. The goal of this work was to obtain novel MDDS composed by IPEC based on different polymethacrylate carriers loaded with BZ and to investigate in vitro drug delivery performance for oral administration. Physicochemical characterizations were studied and preclinical studies in a murine model of acute Chagas disease were also performed. The MDDS composed by BZ-loaded IPEC based on polymethacrylates were obtained by casting solvent followed by wet granulation methods with yields >83%. FT-IR demonstrated ionic interaction between the polyelectrolytes. Confocal microscopy, DSC and PXRD revealed a fraction uniformly distributed of free BZ on the multiparticles. The rheological evaluation of the MDDS showed adequate flow features for their formulation in hard gelatin-capsules. The type and composition of IPEC conditioned the modulation of BZ release and fluid uptake results. MDDS based on more hydrophylic Eudragit® showed very fast dissolution (Q15min > 85%), while an extended release (Q120min ≤ 40%) for the hydrophobic ones was observed. Capsules containing a combination of two MDDS with different release profile of BZ showed promising properties to improve Chagas disease pharmacotherapy in the preliminary in vivo assay performed, in which the BZ-loaded MDDS exhibited efficacy to reduce parasitemia, while decreasing the levels of liver injury markers in comparison to BZ conventional treatment. Multi-kinetic BZ delivery systems developed are interesting pharmaceutical alternatives to improve the treatment of Chagas disease.
Fil: García, Mónica Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Martinelli, Marisa. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada (IPQA), CONICET and Laboratorio de Materiales Poliméricos (LAMAP), Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina; Argentina
Fil: Ponce, Nicolás Eric. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Sanmarco, Liliana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Aoki, Maria del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Manzo, Ruben Hilario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Jimenez Kairuz, Alvaro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
description Interpolyelectrolyte complexes (IPEC) formulated as multiparticulate drug delivery systems (MDDS) are interesting carriers to improve drug’ performance. Benznidazole (BZ) is the first–line drug for Chagas treatment; however, it presents side effects and toxicity, conditioning its efficacy and safety. The goal of this work was to obtain novel MDDS composed by IPEC based on different polymethacrylate carriers loaded with BZ and to investigate in vitro drug delivery performance for oral administration. Physicochemical characterizations were studied and preclinical studies in a murine model of acute Chagas disease were also performed. The MDDS composed by BZ-loaded IPEC based on polymethacrylates were obtained by casting solvent followed by wet granulation methods with yields >83%. FT-IR demonstrated ionic interaction between the polyelectrolytes. Confocal microscopy, DSC and PXRD revealed a fraction uniformly distributed of free BZ on the multiparticles. The rheological evaluation of the MDDS showed adequate flow features for their formulation in hard gelatin-capsules. The type and composition of IPEC conditioned the modulation of BZ release and fluid uptake results. MDDS based on more hydrophylic Eudragit® showed very fast dissolution (Q15min > 85%), while an extended release (Q120min ≤ 40%) for the hydrophobic ones was observed. Capsules containing a combination of two MDDS with different release profile of BZ showed promising properties to improve Chagas disease pharmacotherapy in the preliminary in vivo assay performed, in which the BZ-loaded MDDS exhibited efficacy to reduce parasitemia, while decreasing the levels of liver injury markers in comparison to BZ conventional treatment. Multi-kinetic BZ delivery systems developed are interesting pharmaceutical alternatives to improve the treatment of Chagas disease.
publishDate 2018
dc.date.none.fl_str_mv 2018-07-23
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/11336/92600
García, Mónica Cristina; Martinelli, Marisa; Ponce, Nicolás Eric; Sanmarco, Liliana Maria; Aoki, Maria del Pilar; et al.; Multi-kinetic release of benznidazole-loaded multiparticulate drug delivery systems based on polymethacrylate interpolyelectrolyte complexes; Elsevier Science; European Journal Of Pharmaceutical Sciences; 120; 23-7-2018; 107-122
0928-0987
CONICET Digital
CONICET
url http://hdl.handle.net/11336/92600
identifier_str_mv García, Mónica Cristina; Martinelli, Marisa; Ponce, Nicolás Eric; Sanmarco, Liliana Maria; Aoki, Maria del Pilar; et al.; Multi-kinetic release of benznidazole-loaded multiparticulate drug delivery systems based on polymethacrylate interpolyelectrolyte complexes; Elsevier Science; European Journal Of Pharmaceutical Sciences; 120; 23-7-2018; 107-122
0928-0987
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.sciencedirect.com/science/article/pii/S0928098718301994?via%3Dihub
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejps.2018.04.034
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
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 12.982451

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