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

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dc.creatorJuliana Barbosa Saliba
dc.creatorRodrigo Lambert Oréfice
dc.creatorMeriem Tekaya
dc.creatorLaura Kowalczuk
dc.creatorMin Zhao
dc.creatorFrancine Behar-Cohen
dc.creatorLorena Carla Vieira
dc.creatorGabriella Maria Fernandes Cunha
dc.creatorGisele Rodrigues da Silva
dc.creatorSílvia Ligório Fialho
dc.creatorArmando da Silva Cunha Júnior
dc.creatorElodie Bousquet
dc.creatorMarie-Christine Naud
dc.creatorEliane Ayres
dc.date.accessioned2024-03-05T17:55:14Z
dc.date.accessioned2025-09-09T00:54:29Z
dc.date.available2024-03-05T17:55:14Z
dc.date.issued2016-04
dc.format.mimetypepdf
dc.identifier.doi10.1167/iovs.15-18127
dc.identifier.issn0146-0404
dc.identifier.urihttps://hdl.handle.net/1843/65285
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofInvestigative Ophthalmology & Visual Science
dc.rightsAcesso Aberto
dc.subjectImplantes de medicamento
dc.subjectUveíte
dc.subjectOftalmopatias
dc.subjectUveíte induzido quimicamente
dc.subject.otherPolyurethane
dc.subject.otherImplant
dc.subject.otherSuprachoroidal space
dc.subject.otherDrug delivery
dc.subject.otherEndotoxin-induced uveitis
dc.titleAnti-inflammatory effect of dexamethasone controlled released from anterior suprachoroidal polyurethane implants on endotoxin-induced uveitis in rats
dc.typeArtigo de periódico
local.citation.epage1679
local.citation.issue4
local.citation.spage1671
local.citation.volume57
local.description.resumoPURPOSE. 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.
local.publisher.countryBrasil
local.publisher.departmentENG - DEPARTAMENTO DE ENGENHARIA METALÚRGICA
local.publisher.departmentFAR - DEPARTAMENTO DE PRODUTOS FARMACÊUTICOS
local.publisher.initialsUFMG
local.url.externahttps://iovs.arvojournals.org/article.aspx?articleid=2513119&resultClick=1

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