Anti-inflammatory effect of dexamethasone controlled released from anterior suprachoroidal polyurethane implants on endotoxin-induced uveitis in rats

Detalhes bibliográficos
Autor(a) principal: Juliana Barbosa Saliba
Data de Publicação: 2016
Outros Autores: Rodrigo Lambert Oréfice, Meriem Tekaya, Laura Kowalczuk, Min Zhao, Francine Behar-Cohen, Lorena Carla Vieira, Gabriella Maria Fernandes Cunha, Gisele Rodrigues da Silva, Sílvia Ligório Fialho, Armando da Silva Cunha Júnior, Elodie Bousquet, Marie-Christine Naud, Eliane Ayres
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UFMG
Texto Completo: http://hdl.handle.net/1843/65285
Resumo: PURPOSE. Targeted drug delivery to the ocular tissues remains a challenge. Biodegradable intraocular implants allow prolonged controlled release of drugs directly into the eye. In this study, we evaluated an anterior suprachoroidal polyurethane implant containing dexamethasone polyurethane dispersions (DX-PUD) as a drug delivery system in the rat model of endotoxin-induced uveitis (EIU). METHODS. In vitro drug release was studied using PUD implants containing 8%, 20%, and 30% (wt/wt) DX. Cytotoxicity of the degradation products of DX-PUD was assessed on human ARPE19 cells using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) test. Shortterm ocular biocompatibility of suprachoroidal DX-PUD implants was evaluated in normal rat eyes. Endotoxin-induced uveitis was then induced in rat eyes preimplanted with DX-PUD. Clinical examination was performed at 24 hours; eyes were used to assess inflammatory cell infiltration and macrophage/microglial activation. Cytokine and chemokine expression in the iris/ciliary body and in the retina was investigated using quantitative PCR. Feasibility of anterior suprachoroidal PUD implantation was also tested using postmortem human eyes. RESULTS. A burst release was followed by a sustained controlled release of DX from PUD implants. By-products of the DX-PUD were not toxic to human ARPE-19 cells or to rat ocular tissues. Dexamethasone-PUD implants prevented EIU in rat eyes, reducing inflammatory cell infiltration and inhibiting macrophage/microglial activation. Dexamethasone-PUD downregulated proinflammatory cytokines/chemokines (IL-1b, IL-6, cytokine-induced neutrophil chemoattractant [CINC]) and inducible nitric oxide synthase (iNOS) and upregulated IL-10 anti-inflammatory cytokine. Polyurethane dispersion was successfully implanted into postmortem human eyes. CONCLUSIONS. Dexamethasone-PUD implanted in the anterior suprachoroidal space may be of interest in the treatment of intraocular inflammation.
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spelling 2024-03-05T17:55:14Z2024-03-05T17:55:14Z2016-045741671167910.1167/iovs.15-181270146-0404http://hdl.handle.net/1843/65285PURPOSE. Targeted drug delivery to the ocular tissues remains a challenge. Biodegradable intraocular implants allow prolonged controlled release of drugs directly into the eye. In this study, we evaluated an anterior suprachoroidal polyurethane implant containing dexamethasone polyurethane dispersions (DX-PUD) as a drug delivery system in the rat model of endotoxin-induced uveitis (EIU). METHODS. In vitro drug release was studied using PUD implants containing 8%, 20%, and 30% (wt/wt) DX. Cytotoxicity of the degradation products of DX-PUD was assessed on human ARPE19 cells using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) test. Shortterm ocular biocompatibility of suprachoroidal DX-PUD implants was evaluated in normal rat eyes. Endotoxin-induced uveitis was then induced in rat eyes preimplanted with DX-PUD. Clinical examination was performed at 24 hours; eyes were used to assess inflammatory cell infiltration and macrophage/microglial activation. Cytokine and chemokine expression in the iris/ciliary body and in the retina was investigated using quantitative PCR. Feasibility of anterior suprachoroidal PUD implantation was also tested using postmortem human eyes. RESULTS. A burst release was followed by a sustained controlled release of DX from PUD implants. By-products of the DX-PUD were not toxic to human ARPE-19 cells or to rat ocular tissues. Dexamethasone-PUD implants prevented EIU in rat eyes, reducing inflammatory cell infiltration and inhibiting macrophage/microglial activation. Dexamethasone-PUD downregulated proinflammatory cytokines/chemokines (IL-1b, IL-6, cytokine-induced neutrophil chemoattractant [CINC]) and inducible nitric oxide synthase (iNOS) and upregulated IL-10 anti-inflammatory cytokine. Polyurethane dispersion was successfully implanted into postmortem human eyes. CONCLUSIONS. Dexamethasone-PUD implanted in the anterior suprachoroidal space may be of interest in the treatment of intraocular inflammation.engUniversidade Federal de Minas GeraisUFMGBrasilENG - DEPARTAMENTO DE ENGENHARIA METALÚRGICAFAR - DEPARTAMENTO DE PRODUTOS FARMACÊUTICOSInvestigative Ophthalmology & Visual ScienceImplantes de medicamentoUveíteOftalmopatiasUveíte induzido quimicamentePolyurethaneImplantSuprachoroidal spaceDrug deliveryEndotoxin-induced uveitisAnti-inflammatory effect of dexamethasone controlled released from anterior suprachoroidal polyurethane implants on endotoxin-induced uveitis in ratsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://iovs.arvojournals.org/article.aspx?articleid=2513119&resultClick=1Juliana Barbosa SalibaRodrigo Lambert OréficeMeriem TekayaLaura KowalczukMin ZhaoFrancine Behar-CohenLorena Carla VieiraGabriella Maria Fernandes CunhaGisele Rodrigues da SilvaSílvia Ligório FialhoArmando da Silva Cunha JúniorElodie BousquetMarie-Christine NaudEliane Ayresapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/65285/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALAnti-Inflammatory Effect of Dexamethasone Controlled.pdfAnti-Inflammatory Effect of Dexamethasone Controlled.pdfapplication/pdf979038https://repositorio.ufmg.br/bitstream/1843/65285/2/Anti-Inflammatory%20Effect%20of%20Dexamethasone%20Controlled.pdfb600334c4043b39c7ab6ce12696722daMD521843/652852024-03-05 16:30:40.613oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2024-03-05T19:30:40Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
dc.title.pt_BR.fl_str_mv Anti-inflammatory effect of dexamethasone controlled released from anterior suprachoroidal polyurethane implants on endotoxin-induced uveitis in rats
title Anti-inflammatory effect of dexamethasone controlled released from anterior suprachoroidal polyurethane implants on endotoxin-induced uveitis in rats
spellingShingle Anti-inflammatory effect of dexamethasone controlled released from anterior suprachoroidal polyurethane implants on endotoxin-induced uveitis in rats
Juliana Barbosa Saliba
Polyurethane
Implant
Suprachoroidal space
Drug delivery
Endotoxin-induced uveitis
Implantes de medicamento
Uveíte
Oftalmopatias
Uveíte induzido quimicamente
title_short Anti-inflammatory effect of dexamethasone controlled released from anterior suprachoroidal polyurethane implants on endotoxin-induced uveitis in rats
title_full Anti-inflammatory effect of dexamethasone controlled released from anterior suprachoroidal polyurethane implants on endotoxin-induced uveitis in rats
title_fullStr Anti-inflammatory effect of dexamethasone controlled released from anterior suprachoroidal polyurethane implants on endotoxin-induced uveitis in rats
title_full_unstemmed Anti-inflammatory effect of dexamethasone controlled released from anterior suprachoroidal polyurethane implants on endotoxin-induced uveitis in rats
title_sort Anti-inflammatory effect of dexamethasone controlled released from anterior suprachoroidal polyurethane implants on endotoxin-induced uveitis in rats
author Juliana Barbosa Saliba
author_facet Juliana Barbosa Saliba
Rodrigo Lambert Oréfice
Meriem Tekaya
Laura Kowalczuk
Min Zhao
Francine Behar-Cohen
Lorena Carla Vieira
Gabriella Maria Fernandes Cunha
Gisele Rodrigues da Silva
Sílvia Ligório Fialho
Armando da Silva Cunha Júnior
Elodie Bousquet
Marie-Christine Naud
Eliane Ayres
author_role author
author2 Rodrigo Lambert Oréfice
Meriem Tekaya
Laura Kowalczuk
Min Zhao
Francine Behar-Cohen
Lorena Carla Vieira
Gabriella Maria Fernandes Cunha
Gisele Rodrigues da Silva
Sílvia Ligório Fialho
Armando da Silva Cunha Júnior
Elodie Bousquet
Marie-Christine Naud
Eliane Ayres
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Juliana Barbosa Saliba
Rodrigo Lambert Oréfice
Meriem Tekaya
Laura Kowalczuk
Min Zhao
Francine Behar-Cohen
Lorena Carla Vieira
Gabriella Maria Fernandes Cunha
Gisele Rodrigues da Silva
Sílvia Ligório Fialho
Armando da Silva Cunha Júnior
Elodie Bousquet
Marie-Christine Naud
Eliane Ayres
dc.subject.por.fl_str_mv Polyurethane
Implant
Suprachoroidal space
Drug delivery
Endotoxin-induced uveitis
topic Polyurethane
Implant
Suprachoroidal space
Drug delivery
Endotoxin-induced uveitis
Implantes de medicamento
Uveíte
Oftalmopatias
Uveíte induzido quimicamente
dc.subject.other.pt_BR.fl_str_mv Implantes de medicamento
Uveíte
Oftalmopatias
Uveíte induzido quimicamente
description PURPOSE. Targeted drug delivery to the ocular tissues remains a challenge. Biodegradable intraocular implants allow prolonged controlled release of drugs directly into the eye. In this study, we evaluated an anterior suprachoroidal polyurethane implant containing dexamethasone polyurethane dispersions (DX-PUD) as a drug delivery system in the rat model of endotoxin-induced uveitis (EIU). METHODS. In vitro drug release was studied using PUD implants containing 8%, 20%, and 30% (wt/wt) DX. Cytotoxicity of the degradation products of DX-PUD was assessed on human ARPE19 cells using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) test. Shortterm ocular biocompatibility of suprachoroidal DX-PUD implants was evaluated in normal rat eyes. Endotoxin-induced uveitis was then induced in rat eyes preimplanted with DX-PUD. Clinical examination was performed at 24 hours; eyes were used to assess inflammatory cell infiltration and macrophage/microglial activation. Cytokine and chemokine expression in the iris/ciliary body and in the retina was investigated using quantitative PCR. Feasibility of anterior suprachoroidal PUD implantation was also tested using postmortem human eyes. RESULTS. A burst release was followed by a sustained controlled release of DX from PUD implants. By-products of the DX-PUD were not toxic to human ARPE-19 cells or to rat ocular tissues. Dexamethasone-PUD implants prevented EIU in rat eyes, reducing inflammatory cell infiltration and inhibiting macrophage/microglial activation. Dexamethasone-PUD downregulated proinflammatory cytokines/chemokines (IL-1b, IL-6, cytokine-induced neutrophil chemoattractant [CINC]) and inducible nitric oxide synthase (iNOS) and upregulated IL-10 anti-inflammatory cytokine. Polyurethane dispersion was successfully implanted into postmortem human eyes. CONCLUSIONS. Dexamethasone-PUD implanted in the anterior suprachoroidal space may be of interest in the treatment of intraocular inflammation.
publishDate 2016
dc.date.issued.fl_str_mv 2016-04
dc.date.accessioned.fl_str_mv 2024-03-05T17:55:14Z
dc.date.available.fl_str_mv 2024-03-05T17:55:14Z
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.uri.fl_str_mv http://hdl.handle.net/1843/65285
dc.identifier.doi.pt_BR.fl_str_mv 10.1167/iovs.15-18127
dc.identifier.issn.pt_BR.fl_str_mv 0146-0404
identifier_str_mv 10.1167/iovs.15-18127
0146-0404
url http://hdl.handle.net/1843/65285
dc.language.iso.fl_str_mv eng
language eng
dc.relation.ispartof.none.fl_str_mv Investigative Ophthalmology & Visual Science
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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dc.publisher.none.fl_str_mv Universidade Federal de Minas Gerais
dc.publisher.initials.fl_str_mv UFMG
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv ENG - DEPARTAMENTO DE ENGENHARIA METALÚRGICA
FAR - DEPARTAMENTO DE PRODUTOS FARMACÊUTICOS
publisher.none.fl_str_mv Universidade Federal de Minas Gerais
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFMG
instname:Universidade Federal de Minas Gerais (UFMG)
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