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Type: Artigo de Periódico
Title: Anti-inflammatory effect of dexamethasone controlled released from anterior suprachoroidal polyurethane implants on endotoxin-induced uveitis in rats
Authors: 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
Abstract: 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.
Subject: Implantes de medicamento
Uveíte induzido quimicamente
language: eng Brasil
Publisher: Universidade Federal de Minas Gerais
Publisher Initials: UFMG
metadata.dc.publisher.department: ENG - DEPARTAMENTO DE ENGENHARIA METALÚRGICA
Rights: Acesso Aberto
metadata.dc.identifier.doi: 10.1167/iovs.15-18127
Issue Date: Apr-2016
metadata.dc.relation.ispartof: Investigative Ophthalmology & Visual Science
Appears in Collections:Artigo de Periódico

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