Layered double hydroxide–indomethacin hybrid: A promising biocompatible compound for the treatment of neuroinflammatory diseases

Detalhes bibliográficos
Autor(a) principal: Meneses, Carla Carolina Ferreira
Data de Publicação: 2020
Outros Autores: Sousa, Paulo Robson Monteiro, Pinto, Laine Celestino, Coelho, Gerson Maciel, Silva, Tamires Ferreira da, Ferreira, Luan Oliveira, Gustavo, Kayo Silva, Martins Filho, Arnaldo Jorge, Faial, Kelson do Carmo Freitas, Yamada, Elizabeth Sumi, Lameira, Jerônimo, Jouin, Jenny, Thomas, Philippe, Masson, Oliver, Lopes, Dielly Catrina Favacho, Alves, Cláudio Nahum
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Digital do Instituto Evandro Chagas (Patuá)
DOI: 10.1016/j.jddst.2020.102190
Texto Completo: https://patua.iec.gov.br/handle/iec/4224
Resumo: Indomethacin (INDO) demonstrates therapeutic efficacy in the treatment of neuroinflammatory diseases. Despite its importance as a drug, INDO causes gastrointestinal problems and adverse reactions in the central nervous system (CNS). In this study, we prepared nanoparticles of layered double hydroxide (LDH) loaded with INDO. The structure of the nanohybrid (LDH-INDO) was synthesized via a coprecipitation method, and the nanohybrid was characterized using X-ray powder diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analysis–differential scanning colorimetry (TGA–DSC), field-emission scanning electron microscopy (FE-SEM), and ultraviolet (UV)–vis spectroscopy. Moreover, the drug release profiles of the nanohybrid were investigated using kinetic models. INDO was incorporated within the LDH interlayer space with 50% intercalation. The release of INDO anions from LDH-INDO after 10 h was 90% at pH 4.8 ± 0.02 and 51% at pH 7.4 ± 0.02. The results show that the release profiles follow a pseudo-second-order model. In addition, lipopolysaccharide (LPS)-induced sickness behavior in animals and treatment with INDO and LDH-INDO suggest recovery of the variables (weight and food intake) used in this study. LDH-INDO did not alter hepatic and renal biomarkers. Moreover, LPS increased the number of Iba1+ cells (microgliosis) and caused morphological alterations in these cells in the hippocampus and somatosensory cortex. However, the LPS effect was attenuated after treatment with INDO, both free and LDH-intercalated, in both regions of the brain.
id IEC-2_4bb0354e215d92f1388c3262667a6ad4
oai_identifier_str oai:patua.iec.gov.br:iec/4224
network_acronym_str IEC-2
network_name_str Repositório Digital do Instituto Evandro Chagas (Patuá)
spelling Meneses, Carla Carolina FerreiraSousa, Paulo Robson MonteiroPinto, Laine CelestinoCoelho, Gerson MacielSilva, Tamires Ferreira daFerreira, Luan OliveiraGustavo, Kayo SilvaMartins Filho, Arnaldo JorgeFaial, Kelson do Carmo FreitasYamada, Elizabeth SumiLameira, JerônimoJouin, JennyThomas, PhilippeMasson, OliverLopes, Dielly Catrina FavachoAlves, Cláudio Nahum2021-01-26T14:12:52Z2021-01-26T14:12:52Z2020MENESES, Carla Carolina Ferreira et al. Layered double hydroxide–indomethacin hybrid: A promising biocompatible compound for the treatment of neuroinflammatory diseases. Journal of Drug Delivery Science and Technology, v. xx, 102190, p. xx, Oct. 20201773-2247https://patua.iec.gov.br/handle/iec/422410.1016/j.jddst.2020.102190Indomethacin (INDO) demonstrates therapeutic efficacy in the treatment of neuroinflammatory diseases. Despite its importance as a drug, INDO causes gastrointestinal problems and adverse reactions in the central nervous system (CNS). In this study, we prepared nanoparticles of layered double hydroxide (LDH) loaded with INDO. The structure of the nanohybrid (LDH-INDO) was synthesized via a coprecipitation method, and the nanohybrid was characterized using X-ray powder diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analysis–differential scanning colorimetry (TGA–DSC), field-emission scanning electron microscopy (FE-SEM), and ultraviolet (UV)–vis spectroscopy. Moreover, the drug release profiles of the nanohybrid were investigated using kinetic models. INDO was incorporated within the LDH interlayer space with 50% intercalation. The release of INDO anions from LDH-INDO after 10 h was 90% at pH 4.8 ± 0.02 and 51% at pH 7.4 ± 0.02. The results show that the release profiles follow a pseudo-second-order model. In addition, lipopolysaccharide (LPS)-induced sickness behavior in animals and treatment with INDO and LDH-INDO suggest recovery of the variables (weight and food intake) used in this study. LDH-INDO did not alter hepatic and renal biomarkers. Moreover, LPS increased the number of Iba1+ cells (microgliosis) and caused morphological alterations in these cells in the hippocampus and somatosensory cortex. However, the LPS effect was attenuated after treatment with INDO, both free and LDH-intercalated, in both regions of the brain.Federal University of Pará. Institute of Exact and Natural Sciences. Belém, PA, Brazil.Federal University of Pará. Institute of Exact and Natural Sciences. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Federal University of Pará. Institute of Biological Sciences. Belém, PA, Brazil.Federal University of Pará. Institute of Exact and Natural Sciences. Belém, PA, Brazil.Université de Limoges. Centre Européen de la Céramique. Laboratoire IRCER. Limoges, FranceUniversité de Limoges. Centre Européen de la Céramique. Laboratoire IRCER. Limoges, FranceUniversité de Limoges. Centre Européen de la Céramique. Laboratoire IRCER. Limoges, FranceFederal University of Pará. Institute of Biological Sciences. Belém, PA, Brazil.Federal University of Pará. Institute of Exact and Natural Sciences. Belém, PA, Brazil.engElsevierLayered double hydroxide–indomethacin hybrid: A promising biocompatible compound for the treatment of neuroinflammatory diseasesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleSistema Nervoso CentralIndometacina / administração & dosageminfo:eu-repo/semantics/embargoedAccessreponame:Repositório Digital do Instituto Evandro Chagas (Patuá)instname:Instituto Evandro Chagas (IEC)instacron:IECORIGINALLayered double hydroxide–indomethacin hybrid: A promising biocompatible compound for the treatment of neuroinflammatory diseases.pdfLayered double hydroxide–indomethacin hybrid: A promising biocompatible compound for the treatment of neuroinflammatory diseases.pdfapplication/pdf551083https://patua.iec.gov.br/bitstreams/fbe8bee4-38f8-44ca-b139-7d656c8c332d/downloadc9a9c128e29cac82a5d7fdf3f4e6da73MD51TEXTLayered double hydroxide–indomethacin hybrid: A promising biocompatible compound for the treatment of neuroinflammatory diseases.pdf.txtLayered double hydroxide–indomethacin hybrid: A promising biocompatible compound for the treatment of neuroinflammatory diseases.pdf.txtExtracted texttext/plain2https://patua.iec.gov.br/bitstreams/e40b37c5-c65e-4714-a9ad-1b4aeecd6b78/downloade1c06d85ae7b8b032bef47e42e4c08f9MD55THUMBNAILLayered double hydroxide–indomethacin hybrid: A promising biocompatible compound for the treatment of neuroinflammatory diseases.pdf.jpgLayered double hydroxide–indomethacin hybrid: A promising biocompatible compound for the treatment of neuroinflammatory diseases.pdf.jpgGenerated Thumbnailimage/jpeg3095https://patua.iec.gov.br/bitstreams/e3c5f367-1f16-4c21-a257-52ef58a681df/download71859d578212107f7f8c49a4ce09d9eeMD56LICENSElicense.txtlicense.txttext/plain; charset=utf-82182https://patua.iec.gov.br/bitstreams/8355df66-5eea-4a9e-970f-b3c368963c51/download11832eea31b16df8613079d742d61793MD52iec/42242022-10-20 22:29:35.754oai:patua.iec.gov.br:iec/4224https://patua.iec.gov.brRepositório InstitucionalPUBhttps://patua.iec.gov.br/oai/requestclariceneta@iec.gov.br || Biblioteca@iec.gov.bropendoar:2022-10-20T22:29:35Repositório Digital do Instituto Evandro Chagas (Patuá) - Instituto Evandro Chagas (IEC)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
dc.title.pt_BR.fl_str_mv Layered double hydroxide–indomethacin hybrid: A promising biocompatible compound for the treatment of neuroinflammatory diseases
title Layered double hydroxide–indomethacin hybrid: A promising biocompatible compound for the treatment of neuroinflammatory diseases
spellingShingle Layered double hydroxide–indomethacin hybrid: A promising biocompatible compound for the treatment of neuroinflammatory diseases
Layered double hydroxide–indomethacin hybrid: A promising biocompatible compound for the treatment of neuroinflammatory diseases
Meneses, Carla Carolina Ferreira
Sistema Nervoso Central
Indometacina / administração & dosagem
Meneses, Carla Carolina Ferreira
Sistema Nervoso Central
Indometacina / administração & dosagem
title_short Layered double hydroxide–indomethacin hybrid: A promising biocompatible compound for the treatment of neuroinflammatory diseases
title_full Layered double hydroxide–indomethacin hybrid: A promising biocompatible compound for the treatment of neuroinflammatory diseases
title_fullStr Layered double hydroxide–indomethacin hybrid: A promising biocompatible compound for the treatment of neuroinflammatory diseases
Layered double hydroxide–indomethacin hybrid: A promising biocompatible compound for the treatment of neuroinflammatory diseases
title_full_unstemmed Layered double hydroxide–indomethacin hybrid: A promising biocompatible compound for the treatment of neuroinflammatory diseases
Layered double hydroxide–indomethacin hybrid: A promising biocompatible compound for the treatment of neuroinflammatory diseases
title_sort Layered double hydroxide–indomethacin hybrid: A promising biocompatible compound for the treatment of neuroinflammatory diseases
author Meneses, Carla Carolina Ferreira
author_facet Meneses, Carla Carolina Ferreira
Meneses, Carla Carolina Ferreira
Sousa, Paulo Robson Monteiro
Pinto, Laine Celestino
Coelho, Gerson Maciel
Silva, Tamires Ferreira da
Ferreira, Luan Oliveira
Gustavo, Kayo Silva
Martins Filho, Arnaldo Jorge
Faial, Kelson do Carmo Freitas
Yamada, Elizabeth Sumi
Lameira, Jerônimo
Jouin, Jenny
Thomas, Philippe
Masson, Oliver
Lopes, Dielly Catrina Favacho
Alves, Cláudio Nahum
Sousa, Paulo Robson Monteiro
Pinto, Laine Celestino
Coelho, Gerson Maciel
Silva, Tamires Ferreira da
Ferreira, Luan Oliveira
Gustavo, Kayo Silva
Martins Filho, Arnaldo Jorge
Faial, Kelson do Carmo Freitas
Yamada, Elizabeth Sumi
Lameira, Jerônimo
Jouin, Jenny
Thomas, Philippe
Masson, Oliver
Lopes, Dielly Catrina Favacho
Alves, Cláudio Nahum
author_role author
author2 Sousa, Paulo Robson Monteiro
Pinto, Laine Celestino
Coelho, Gerson Maciel
Silva, Tamires Ferreira da
Ferreira, Luan Oliveira
Gustavo, Kayo Silva
Martins Filho, Arnaldo Jorge
Faial, Kelson do Carmo Freitas
Yamada, Elizabeth Sumi
Lameira, Jerônimo
Jouin, Jenny
Thomas, Philippe
Masson, Oliver
Lopes, Dielly Catrina Favacho
Alves, Cláudio Nahum
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Meneses, Carla Carolina Ferreira
Sousa, Paulo Robson Monteiro
Pinto, Laine Celestino
Coelho, Gerson Maciel
Silva, Tamires Ferreira da
Ferreira, Luan Oliveira
Gustavo, Kayo Silva
Martins Filho, Arnaldo Jorge
Faial, Kelson do Carmo Freitas
Yamada, Elizabeth Sumi
Lameira, Jerônimo
Jouin, Jenny
Thomas, Philippe
Masson, Oliver
Lopes, Dielly Catrina Favacho
Alves, Cláudio Nahum
dc.subject.decsPrimary.pt_BR.fl_str_mv Sistema Nervoso Central
Indometacina / administração & dosagem
topic Sistema Nervoso Central
Indometacina / administração & dosagem
description Indomethacin (INDO) demonstrates therapeutic efficacy in the treatment of neuroinflammatory diseases. Despite its importance as a drug, INDO causes gastrointestinal problems and adverse reactions in the central nervous system (CNS). In this study, we prepared nanoparticles of layered double hydroxide (LDH) loaded with INDO. The structure of the nanohybrid (LDH-INDO) was synthesized via a coprecipitation method, and the nanohybrid was characterized using X-ray powder diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analysis–differential scanning colorimetry (TGA–DSC), field-emission scanning electron microscopy (FE-SEM), and ultraviolet (UV)–vis spectroscopy. Moreover, the drug release profiles of the nanohybrid were investigated using kinetic models. INDO was incorporated within the LDH interlayer space with 50% intercalation. The release of INDO anions from LDH-INDO after 10 h was 90% at pH 4.8 ± 0.02 and 51% at pH 7.4 ± 0.02. The results show that the release profiles follow a pseudo-second-order model. In addition, lipopolysaccharide (LPS)-induced sickness behavior in animals and treatment with INDO and LDH-INDO suggest recovery of the variables (weight and food intake) used in this study. LDH-INDO did not alter hepatic and renal biomarkers. Moreover, LPS increased the number of Iba1+ cells (microgliosis) and caused morphological alterations in these cells in the hippocampus and somatosensory cortex. However, the LPS effect was attenuated after treatment with INDO, both free and LDH-intercalated, in both regions of the brain.
publishDate 2020
dc.date.issued.fl_str_mv 2020
dc.date.accessioned.fl_str_mv 2021-01-26T14:12:52Z
dc.date.available.fl_str_mv 2021-01-26T14:12:52Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv MENESES, Carla Carolina Ferreira et al. Layered double hydroxide–indomethacin hybrid: A promising biocompatible compound for the treatment of neuroinflammatory diseases. Journal of Drug Delivery Science and Technology, v. xx, 102190, p. xx, Oct. 2020
dc.identifier.uri.fl_str_mv https://patua.iec.gov.br/handle/iec/4224
dc.identifier.issn.-.fl_str_mv 1773-2247
dc.identifier.doi.-.fl_str_mv 10.1016/j.jddst.2020.102190
identifier_str_mv MENESES, Carla Carolina Ferreira et al. Layered double hydroxide–indomethacin hybrid: A promising biocompatible compound for the treatment of neuroinflammatory diseases. Journal of Drug Delivery Science and Technology, v. xx, 102190, p. xx, Oct. 2020
1773-2247
10.1016/j.jddst.2020.102190
url https://patua.iec.gov.br/handle/iec/4224
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/embargoedAccess
eu_rights_str_mv embargoedAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Digital do Instituto Evandro Chagas (Patuá)
instname:Instituto Evandro Chagas (IEC)
instacron:IEC
instname_str Instituto Evandro Chagas (IEC)
instacron_str IEC
institution IEC
reponame_str Repositório Digital do Instituto Evandro Chagas (Patuá)
collection Repositório Digital do Instituto Evandro Chagas (Patuá)
bitstream.url.fl_str_mv https://patua.iec.gov.br/bitstreams/fbe8bee4-38f8-44ca-b139-7d656c8c332d/download
https://patua.iec.gov.br/bitstreams/e40b37c5-c65e-4714-a9ad-1b4aeecd6b78/download
https://patua.iec.gov.br/bitstreams/e3c5f367-1f16-4c21-a257-52ef58a681df/download
https://patua.iec.gov.br/bitstreams/8355df66-5eea-4a9e-970f-b3c368963c51/download
bitstream.checksum.fl_str_mv c9a9c128e29cac82a5d7fdf3f4e6da73
e1c06d85ae7b8b032bef47e42e4c08f9
71859d578212107f7f8c49a4ce09d9ee
11832eea31b16df8613079d742d61793
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositório Digital do Instituto Evandro Chagas (Patuá) - Instituto Evandro Chagas (IEC)
repository.mail.fl_str_mv clariceneta@iec.gov.br || Biblioteca@iec.gov.br
_version_ 1822222400956137472
dc.identifier.doi.none.fl_str_mv 10.1016/j.jddst.2020.102190