Systemic Exposure, Tissue Distribution, and Disease Evolution of a High Solubility Ciprofloxacin−Aluminum Complex in a Murine Model of Septicemia Induced by Salmonella enterica Ser...

Autores
Breda, Susana Andrea; Guzman, Maria Laura; Confalonieri, Alejandra; Gonzalez, Claudia; Sparo, Monica; Manzo, Ruben Hilario; Sanchez Bruni, Sergio Fabian; Olivera, Maria Eugenia
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A new pharmaceutical derivative obtained by stoichiometric complexation of ciprofloxacin (CIP) with aluminum (CIP-complex) has been investigated and reported in this study. Such product has high solubility in the gastrointestinal pH range and was successful in the development of optimized formulations while maintaining its antimicrobial potency. The systemic exposure, tissue distribution, and the disease evolution after given CIP-complex were assessed. The systemic exposure and distribution in intestines, lungs, and kidneys after a single intragastric administration of CIP-complex and CIP given alone, used as reference, were performed in Balb-C mice at a dose of 5 mg CIP/kg. For the assessment of the disease evolution assay, mice were infected with a virulent strain of Salmonella enterica serotype Enteritidis and treated intragastrically once or twice daily during 5 consecutive days with solutions of CIP-complex or the reference. Clinical follow up and survival was measured during 15 days post inoculation and health state was scored during this period from 0 to 5. CIP-complex showed a 32% increase in Cmax, an earlier Tmax, and a smaller AUC0–12 than the reference. Maximum tissue concentrations (0.5–1 h) were significantly higher in CIP-complex (447% in intestine, 93% in kidney, and 44% in lungs). In the infection model used in this study, survival in CIP-complex versus CIP groups was 40% versus 20% (twice-daily administration) and 30% versus 0% (once-daily administration). Health state of the survivors of CIP-complex group (5/5) was higher than CIP group (3/5). The greater effectiveness of CIP-complex is attributed to the higher levels of CIP in the intestine. Our results supported the fact that CIP-complex is a promising candidate to develop dose-efficient formulations of CIP for oral administration.
Fil: Breda, Susana Andrea. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Unidad de Investigacion y Desarrollo en Tecnologia Farmaceutica; Argentina
Fil: Guzman, Maria Laura. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Unidad de Investigacion y Desarrollo en Tecnologia Farmaceutica; Argentina
Fil: Confalonieri, Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; Argentina
Fil: Gonzalez, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; Argentina
Fil: Sparo, Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; Argentina
Fil: Manzo, Ruben Hilario. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Unidad de Investigacion y Desarrollo en Tecnologia Farmaceutica; Argentina
Fil: Sanchez Bruni, Sergio Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; Argentina
Fil: Olivera, Maria Eugenia. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Unidad de Investigacion y Desarrollo en Tecnologia Farmaceutica; Argentina
Materia
Ciprofloxacin
Biodistribución
Complejo Aluminio
Farmacocinética
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/4694
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/4694
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Systemic Exposure, Tissue Distribution, and Disease Evolution of a High Solubility Ciprofloxacin−Aluminum Complex in a Murine Model of Septicemia Induced by Salmonella enterica Serotype EnteritidisBreda, Susana AndreaGuzman, Maria LauraConfalonieri, AlejandraGonzalez, ClaudiaSparo, MonicaManzo, Ruben HilarioSanchez Bruni, Sergio FabianOlivera, Maria EugeniaCiprofloxacinBiodistribuciónComplejo AluminioFarmacocinéticahttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4A new pharmaceutical derivative obtained by stoichiometric complexation of ciprofloxacin (CIP) with aluminum (CIP-complex) has been investigated and reported in this study. Such product has high solubility in the gastrointestinal pH range and was successful in the development of optimized formulations while maintaining its antimicrobial potency. The systemic exposure, tissue distribution, and the disease evolution after given CIP-complex were assessed. The systemic exposure and distribution in intestines, lungs, and kidneys after a single intragastric administration of CIP-complex and CIP given alone, used as reference, were performed in Balb-C mice at a dose of 5 mg CIP/kg. For the assessment of the disease evolution assay, mice were infected with a virulent strain of Salmonella enterica serotype Enteritidis and treated intragastrically once or twice daily during 5 consecutive days with solutions of CIP-complex or the reference. Clinical follow up and survival was measured during 15 days post inoculation and health state was scored during this period from 0 to 5. CIP-complex showed a 32% increase in Cmax, an earlier Tmax, and a smaller AUC0–12 than the reference. Maximum tissue concentrations (0.5–1 h) were significantly higher in CIP-complex (447% in intestine, 93% in kidney, and 44% in lungs). In the infection model used in this study, survival in CIP-complex versus CIP groups was 40% versus 20% (twice-daily administration) and 30% versus 0% (once-daily administration). Health state of the survivors of CIP-complex group (5/5) was higher than CIP group (3/5). The greater effectiveness of CIP-complex is attributed to the higher levels of CIP in the intestine. Our results supported the fact that CIP-complex is a promising candidate to develop dose-efficient formulations of CIP for oral administration.Fil: Breda, Susana Andrea. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Unidad de Investigacion y Desarrollo en Tecnologia Farmaceutica; ArgentinaFil: Guzman, Maria Laura. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Unidad de Investigacion y Desarrollo en Tecnologia Farmaceutica; ArgentinaFil: Confalonieri, Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; ArgentinaFil: Gonzalez, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; ArgentinaFil: Sparo, Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; ArgentinaFil: Manzo, Ruben Hilario. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Unidad de Investigacion y Desarrollo en Tecnologia Farmaceutica; ArgentinaFil: Sanchez Bruni, Sergio Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; ArgentinaFil: Olivera, Maria Eugenia. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Unidad de Investigacion y Desarrollo en Tecnologia Farmaceutica; ArgentinaAmerican Chemical Society2013-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/4694Breda, Susana Andrea; Guzman, Maria Laura; Confalonieri, Alejandra; Gonzalez, Claudia; Sparo, Monica; et al.; Systemic Exposure, Tissue Distribution, and Disease Evolution of a High Solubility Ciprofloxacin−Aluminum Complex in a Murine Model of Septicemia Induced by Salmonella enterica Serotype Enteritidis; American Chemical Society; Molecular Pharmaceutics; 10; 2; 2-2013; 598-6051543-8384enginfo:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/abs/10.1021/mp300356ainfo:eu-repo/semantics/altIdentifier/doi/10.1021/mp300356ainfo:eu-repo/semantics/altIdentifier/issn/1543-8384info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-05T10:39:59Zoai:ri.conicet.gov.ar:11336/4694instacron: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:34982025-11-05 10:40:00.239CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Systemic Exposure, Tissue Distribution, and Disease Evolution of a High Solubility Ciprofloxacin−Aluminum Complex in a Murine Model of Septicemia Induced by Salmonella enterica Serotype Enteritidis
title Systemic Exposure, Tissue Distribution, and Disease Evolution of a High Solubility Ciprofloxacin−Aluminum Complex in a Murine Model of Septicemia Induced by Salmonella enterica Serotype Enteritidis
spellingShingle Systemic Exposure, Tissue Distribution, and Disease Evolution of a High Solubility Ciprofloxacin−Aluminum Complex in a Murine Model of Septicemia Induced by Salmonella enterica Serotype Enteritidis
Breda, Susana Andrea
Ciprofloxacin
Biodistribución
Complejo Aluminio
Farmacocinética
title_short Systemic Exposure, Tissue Distribution, and Disease Evolution of a High Solubility Ciprofloxacin−Aluminum Complex in a Murine Model of Septicemia Induced by Salmonella enterica Serotype Enteritidis
title_full Systemic Exposure, Tissue Distribution, and Disease Evolution of a High Solubility Ciprofloxacin−Aluminum Complex in a Murine Model of Septicemia Induced by Salmonella enterica Serotype Enteritidis
title_fullStr Systemic Exposure, Tissue Distribution, and Disease Evolution of a High Solubility Ciprofloxacin−Aluminum Complex in a Murine Model of Septicemia Induced by Salmonella enterica Serotype Enteritidis
title_full_unstemmed Systemic Exposure, Tissue Distribution, and Disease Evolution of a High Solubility Ciprofloxacin−Aluminum Complex in a Murine Model of Septicemia Induced by Salmonella enterica Serotype Enteritidis
title_sort Systemic Exposure, Tissue Distribution, and Disease Evolution of a High Solubility Ciprofloxacin−Aluminum Complex in a Murine Model of Septicemia Induced by Salmonella enterica Serotype Enteritidis
dc.creator.none.fl_str_mv Breda, Susana Andrea
Guzman, Maria Laura
Confalonieri, Alejandra
Gonzalez, Claudia
Sparo, Monica
Manzo, Ruben Hilario
Sanchez Bruni, Sergio Fabian
Olivera, Maria Eugenia
author Breda, Susana Andrea
author_facet Breda, Susana Andrea
Guzman, Maria Laura
Confalonieri, Alejandra
Gonzalez, Claudia
Sparo, Monica
Manzo, Ruben Hilario
Sanchez Bruni, Sergio Fabian
Olivera, Maria Eugenia
author_role author
author2 Guzman, Maria Laura
Confalonieri, Alejandra
Gonzalez, Claudia
Sparo, Monica
Manzo, Ruben Hilario
Sanchez Bruni, Sergio Fabian
Olivera, Maria Eugenia
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciprofloxacin
Biodistribución
Complejo Aluminio
Farmacocinética
topic Ciprofloxacin
Biodistribución
Complejo Aluminio
Farmacocinética
purl_subject.fl_str_mv https://purl.org/becyt/ford/4.3
https://purl.org/becyt/ford/4
dc.description.none.fl_txt_mv A new pharmaceutical derivative obtained by stoichiometric complexation of ciprofloxacin (CIP) with aluminum (CIP-complex) has been investigated and reported in this study. Such product has high solubility in the gastrointestinal pH range and was successful in the development of optimized formulations while maintaining its antimicrobial potency. The systemic exposure, tissue distribution, and the disease evolution after given CIP-complex were assessed. The systemic exposure and distribution in intestines, lungs, and kidneys after a single intragastric administration of CIP-complex and CIP given alone, used as reference, were performed in Balb-C mice at a dose of 5 mg CIP/kg. For the assessment of the disease evolution assay, mice were infected with a virulent strain of Salmonella enterica serotype Enteritidis and treated intragastrically once or twice daily during 5 consecutive days with solutions of CIP-complex or the reference. Clinical follow up and survival was measured during 15 days post inoculation and health state was scored during this period from 0 to 5. CIP-complex showed a 32% increase in Cmax, an earlier Tmax, and a smaller AUC0–12 than the reference. Maximum tissue concentrations (0.5–1 h) were significantly higher in CIP-complex (447% in intestine, 93% in kidney, and 44% in lungs). In the infection model used in this study, survival in CIP-complex versus CIP groups was 40% versus 20% (twice-daily administration) and 30% versus 0% (once-daily administration). Health state of the survivors of CIP-complex group (5/5) was higher than CIP group (3/5). The greater effectiveness of CIP-complex is attributed to the higher levels of CIP in the intestine. Our results supported the fact that CIP-complex is a promising candidate to develop dose-efficient formulations of CIP for oral administration.
Fil: Breda, Susana Andrea. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Unidad de Investigacion y Desarrollo en Tecnologia Farmaceutica; Argentina
Fil: Guzman, Maria Laura. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Unidad de Investigacion y Desarrollo en Tecnologia Farmaceutica; Argentina
Fil: Confalonieri, Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; Argentina
Fil: Gonzalez, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; Argentina
Fil: Sparo, Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; Argentina
Fil: Manzo, Ruben Hilario. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Unidad de Investigacion y Desarrollo en Tecnologia Farmaceutica; Argentina
Fil: Sanchez Bruni, Sergio Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; Argentina
Fil: Olivera, Maria Eugenia. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Unidad de Investigacion y Desarrollo en Tecnologia Farmaceutica; Argentina
description A new pharmaceutical derivative obtained by stoichiometric complexation of ciprofloxacin (CIP) with aluminum (CIP-complex) has been investigated and reported in this study. Such product has high solubility in the gastrointestinal pH range and was successful in the development of optimized formulations while maintaining its antimicrobial potency. The systemic exposure, tissue distribution, and the disease evolution after given CIP-complex were assessed. The systemic exposure and distribution in intestines, lungs, and kidneys after a single intragastric administration of CIP-complex and CIP given alone, used as reference, were performed in Balb-C mice at a dose of 5 mg CIP/kg. For the assessment of the disease evolution assay, mice were infected with a virulent strain of Salmonella enterica serotype Enteritidis and treated intragastrically once or twice daily during 5 consecutive days with solutions of CIP-complex or the reference. Clinical follow up and survival was measured during 15 days post inoculation and health state was scored during this period from 0 to 5. CIP-complex showed a 32% increase in Cmax, an earlier Tmax, and a smaller AUC0–12 than the reference. Maximum tissue concentrations (0.5–1 h) were significantly higher in CIP-complex (447% in intestine, 93% in kidney, and 44% in lungs). In the infection model used in this study, survival in CIP-complex versus CIP groups was 40% versus 20% (twice-daily administration) and 30% versus 0% (once-daily administration). Health state of the survivors of CIP-complex group (5/5) was higher than CIP group (3/5). The greater effectiveness of CIP-complex is attributed to the higher levels of CIP in the intestine. Our results supported the fact that CIP-complex is a promising candidate to develop dose-efficient formulations of CIP for oral administration.
publishDate 2013
dc.date.none.fl_str_mv 2013-02
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/11336/4694
Breda, Susana Andrea; Guzman, Maria Laura; Confalonieri, Alejandra; Gonzalez, Claudia; Sparo, Monica; et al.; Systemic Exposure, Tissue Distribution, and Disease Evolution of a High Solubility Ciprofloxacin−Aluminum Complex in a Murine Model of Septicemia Induced by Salmonella enterica Serotype Enteritidis; American Chemical Society; Molecular Pharmaceutics; 10; 2; 2-2013; 598-605
1543-8384
url http://hdl.handle.net/11336/4694
identifier_str_mv Breda, Susana Andrea; Guzman, Maria Laura; Confalonieri, Alejandra; Gonzalez, Claudia; Sparo, Monica; et al.; Systemic Exposure, Tissue Distribution, and Disease Evolution of a High Solubility Ciprofloxacin−Aluminum Complex in a Murine Model of Septicemia Induced by Salmonella enterica Serotype Enteritidis; American Chemical Society; Molecular Pharmaceutics; 10; 2; 2-2013; 598-605
1543-8384
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/abs/10.1021/mp300356a
info:eu-repo/semantics/altIdentifier/doi/10.1021/mp300356a
info:eu-repo/semantics/altIdentifier/issn/1543-8384
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
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 13.087074

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