Intestinal uptake and toxicity evaluation of acetazolamide and its multicomponent complexes with Hidroxypropyl-β-Cyclodextrin in rats

Autores
Mora, Maria Julia; Petiti, Juan Pablo; Longhi, Marcela Raquel; Torres, Alicia Ines; Granero, Gladys Ester
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Large oral doses of ACZ lower the intraocular pressure (IOP), but usually lead to a multitude of systemic side effects, including gastrointestinal upset. The present study was undertaken to evaluate the effect of ACZ on the histological structure of rat duodenal mucosa and to assess a possible protective role of the complex formation of ACZ with HP-β-CD, either separately or in combination with a third compound, on the gut epithelial layer by histological and ultrastructural examinations of sections of rat duodenum exposed to ACZ or its formulations. In addition, the transport process of ACZ and its binary or ternary complexes across the duodenal mucosa by means of the single-pass intestinal perfusion (SPIP) method in rats was evaluated. Evidence was found that ACZ alters intestinal permeability and induces damage to the rat small intestine. In contrast, ACZ-induced intestinal injury may be abrogated by ACZ complexation. In addition, the complexation of ACZ with HP-β-CD, alone or in combination with a third compound, facilitated significant levels of ACZ uptake across the rat duodenal segment. Ternary complexes of ACZ with HP-β-CD in combination with TEA (triethanolamine) or calcium ions were found to provide an excellent approach that enabled an increased apparent permeability of ACZ across the duodenal epithelium, with a concomitant ability to preserve the integrity of the gut epithelium from ACZ-induced injury. These results could be useful for the design and development of novel ACZ formulations that can reduce GI toxicity, while still maintaining their essential therapeutic efficacies.
Fil: Mora, Maria Julia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Unidad de Investigacion y Desarrollo En Tecnologia Farmaceutica; Argentina
Fil: Petiti, Juan Pablo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones En Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Fil: Longhi, Marcela Raquel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Unidad de Investigacion y Desarrollo En Tecnologia Farmaceutica; Argentina
Fil: Torres, Alicia Ines. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones En Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Fil: Granero, Gladys Ester. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Unidad de Investigacion y Desarrollo En Tecnologia Farmaceutica; Argentina
Materia
Acetozolamide
Cyclodextrins
Multicomponent Complexes
Gut Intestinal Epithelium Injury
Permeability
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:11336/11502
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/11502
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Intestinal uptake and toxicity evaluation of acetazolamide and its multicomponent complexes with Hidroxypropyl-β-Cyclodextrin in ratsMora, Maria JuliaPetiti, Juan PabloLonghi, Marcela RaquelTorres, Alicia InesGranero, Gladys EsterAcetozolamideCyclodextrinsMulticomponent ComplexesGut Intestinal Epithelium InjuryPermeabilityhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Large oral doses of ACZ lower the intraocular pressure (IOP), but usually lead to a multitude of systemic side effects, including gastrointestinal upset. The present study was undertaken to evaluate the effect of ACZ on the histological structure of rat duodenal mucosa and to assess a possible protective role of the complex formation of ACZ with HP-β-CD, either separately or in combination with a third compound, on the gut epithelial layer by histological and ultrastructural examinations of sections of rat duodenum exposed to ACZ or its formulations. In addition, the transport process of ACZ and its binary or ternary complexes across the duodenal mucosa by means of the single-pass intestinal perfusion (SPIP) method in rats was evaluated. Evidence was found that ACZ alters intestinal permeability and induces damage to the rat small intestine. In contrast, ACZ-induced intestinal injury may be abrogated by ACZ complexation. In addition, the complexation of ACZ with HP-β-CD, alone or in combination with a third compound, facilitated significant levels of ACZ uptake across the rat duodenal segment. Ternary complexes of ACZ with HP-β-CD in combination with TEA (triethanolamine) or calcium ions were found to provide an excellent approach that enabled an increased apparent permeability of ACZ across the duodenal epithelium, with a concomitant ability to preserve the integrity of the gut epithelium from ACZ-induced injury. These results could be useful for the design and development of novel ACZ formulations that can reduce GI toxicity, while still maintaining their essential therapeutic efficacies.Fil: Mora, Maria Julia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Unidad de Investigacion y Desarrollo En Tecnologia Farmaceutica; ArgentinaFil: Petiti, Juan Pablo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones En Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; ArgentinaFil: Longhi, Marcela Raquel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Unidad de Investigacion y Desarrollo En Tecnologia Farmaceutica; ArgentinaFil: Torres, Alicia Ines. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones En Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; ArgentinaFil: Granero, Gladys Ester. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Unidad de Investigacion y Desarrollo En Tecnologia Farmaceutica; ArgentinaElsevier Science2015-01info: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/11336/11502Mora, Maria Julia; Petiti, Juan Pablo; Longhi, Marcela Raquel; Torres, Alicia Ines; Granero, Gladys Ester; Intestinal uptake and toxicity evaluation of acetazolamide and its multicomponent complexes with Hidroxypropyl-β-Cyclodextrin in rats; Elsevier Science; International Journal Of Pharmaceutics; 478; 1; 1-2015; 258-2670378-5173enginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ijpharm.2014.11.027info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0378517314008308info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:28:01Zoai:ri.conicet.gov.ar:11336/11502instacron: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:34982025-09-29 10:28:01.508CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Intestinal uptake and toxicity evaluation of acetazolamide and its multicomponent complexes with Hidroxypropyl-β-Cyclodextrin in rats
title Intestinal uptake and toxicity evaluation of acetazolamide and its multicomponent complexes with Hidroxypropyl-β-Cyclodextrin in rats
spellingShingle Intestinal uptake and toxicity evaluation of acetazolamide and its multicomponent complexes with Hidroxypropyl-β-Cyclodextrin in rats
Mora, Maria Julia
Acetozolamide
Cyclodextrins
Multicomponent Complexes
Gut Intestinal Epithelium Injury
Permeability
title_short Intestinal uptake and toxicity evaluation of acetazolamide and its multicomponent complexes with Hidroxypropyl-β-Cyclodextrin in rats
title_full Intestinal uptake and toxicity evaluation of acetazolamide and its multicomponent complexes with Hidroxypropyl-β-Cyclodextrin in rats
title_fullStr Intestinal uptake and toxicity evaluation of acetazolamide and its multicomponent complexes with Hidroxypropyl-β-Cyclodextrin in rats
title_full_unstemmed Intestinal uptake and toxicity evaluation of acetazolamide and its multicomponent complexes with Hidroxypropyl-β-Cyclodextrin in rats
title_sort Intestinal uptake and toxicity evaluation of acetazolamide and its multicomponent complexes with Hidroxypropyl-β-Cyclodextrin in rats
dc.creator.none.fl_str_mv Mora, Maria Julia
Petiti, Juan Pablo
Longhi, Marcela Raquel
Torres, Alicia Ines
Granero, Gladys Ester
author Mora, Maria Julia
author_facet Mora, Maria Julia
Petiti, Juan Pablo
Longhi, Marcela Raquel
Torres, Alicia Ines
Granero, Gladys Ester
author_role author
author2 Petiti, Juan Pablo
Longhi, Marcela Raquel
Torres, Alicia Ines
Granero, Gladys Ester
author2_role author
author
author
author
dc.subject.none.fl_str_mv Acetozolamide
Cyclodextrins
Multicomponent Complexes
Gut Intestinal Epithelium Injury
Permeability
topic Acetozolamide
Cyclodextrins
Multicomponent Complexes
Gut Intestinal Epithelium Injury
Permeability
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Large oral doses of ACZ lower the intraocular pressure (IOP), but usually lead to a multitude of systemic side effects, including gastrointestinal upset. The present study was undertaken to evaluate the effect of ACZ on the histological structure of rat duodenal mucosa and to assess a possible protective role of the complex formation of ACZ with HP-β-CD, either separately or in combination with a third compound, on the gut epithelial layer by histological and ultrastructural examinations of sections of rat duodenum exposed to ACZ or its formulations. In addition, the transport process of ACZ and its binary or ternary complexes across the duodenal mucosa by means of the single-pass intestinal perfusion (SPIP) method in rats was evaluated. Evidence was found that ACZ alters intestinal permeability and induces damage to the rat small intestine. In contrast, ACZ-induced intestinal injury may be abrogated by ACZ complexation. In addition, the complexation of ACZ with HP-β-CD, alone or in combination with a third compound, facilitated significant levels of ACZ uptake across the rat duodenal segment. Ternary complexes of ACZ with HP-β-CD in combination with TEA (triethanolamine) or calcium ions were found to provide an excellent approach that enabled an increased apparent permeability of ACZ across the duodenal epithelium, with a concomitant ability to preserve the integrity of the gut epithelium from ACZ-induced injury. These results could be useful for the design and development of novel ACZ formulations that can reduce GI toxicity, while still maintaining their essential therapeutic efficacies.
Fil: Mora, Maria Julia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Unidad de Investigacion y Desarrollo En Tecnologia Farmaceutica; Argentina
Fil: Petiti, Juan Pablo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones En Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Fil: Longhi, Marcela Raquel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Unidad de Investigacion y Desarrollo En Tecnologia Farmaceutica; Argentina
Fil: Torres, Alicia Ines. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones En Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Fil: Granero, Gladys Ester. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Unidad de Investigacion y Desarrollo En Tecnologia Farmaceutica; Argentina
description Large oral doses of ACZ lower the intraocular pressure (IOP), but usually lead to a multitude of systemic side effects, including gastrointestinal upset. The present study was undertaken to evaluate the effect of ACZ on the histological structure of rat duodenal mucosa and to assess a possible protective role of the complex formation of ACZ with HP-β-CD, either separately or in combination with a third compound, on the gut epithelial layer by histological and ultrastructural examinations of sections of rat duodenum exposed to ACZ or its formulations. In addition, the transport process of ACZ and its binary or ternary complexes across the duodenal mucosa by means of the single-pass intestinal perfusion (SPIP) method in rats was evaluated. Evidence was found that ACZ alters intestinal permeability and induces damage to the rat small intestine. In contrast, ACZ-induced intestinal injury may be abrogated by ACZ complexation. In addition, the complexation of ACZ with HP-β-CD, alone or in combination with a third compound, facilitated significant levels of ACZ uptake across the rat duodenal segment. Ternary complexes of ACZ with HP-β-CD in combination with TEA (triethanolamine) or calcium ions were found to provide an excellent approach that enabled an increased apparent permeability of ACZ across the duodenal epithelium, with a concomitant ability to preserve the integrity of the gut epithelium from ACZ-induced injury. These results could be useful for the design and development of novel ACZ formulations that can reduce GI toxicity, while still maintaining their essential therapeutic efficacies.
publishDate 2015
dc.date.none.fl_str_mv 2015-01
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/11336/11502
Mora, Maria Julia; Petiti, Juan Pablo; Longhi, Marcela Raquel; Torres, Alicia Ines; Granero, Gladys Ester; Intestinal uptake and toxicity evaluation of acetazolamide and its multicomponent complexes with Hidroxypropyl-β-Cyclodextrin in rats; Elsevier Science; International Journal Of Pharmaceutics; 478; 1; 1-2015; 258-267
0378-5173
url http://hdl.handle.net/11336/11502
identifier_str_mv Mora, Maria Julia; Petiti, Juan Pablo; Longhi, Marcela Raquel; Torres, Alicia Ines; Granero, Gladys Ester; Intestinal uptake and toxicity evaluation of acetazolamide and its multicomponent complexes with Hidroxypropyl-β-Cyclodextrin in rats; Elsevier Science; International Journal Of Pharmaceutics; 478; 1; 1-2015; 258-267
0378-5173
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ijpharm.2014.11.027
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0378517314008308
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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