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http://hdl.handle.net/1843/65285| Tipo: | Artigo de Periódico |
| Título: | Anti-inflammatory effect of dexamethasone controlled released from anterior suprachoroidal polyurethane implants on endotoxin-induced uveitis in rats |
| Autor(es): | 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 |
| 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. |
| Assunto: | Implantes de medicamento Uveíte Oftalmopatias Uveíte induzido quimicamente |
| Idioma: | eng |
| País: | Brasil |
| Editor: | Universidade Federal de Minas Gerais |
| Sigla da Instituição: | UFMG |
| Departamento: | ENG - DEPARTAMENTO DE ENGENHARIA METALÚRGICA FAR - DEPARTAMENTO DE PRODUTOS FARMACÊUTICOS |
| Tipo de Acesso: | Acesso Aberto |
| Identificador DOI: | 10.1167/iovs.15-18127 |
| URI: | http://hdl.handle.net/1843/65285 |
| Data do documento: | Abr-2016 |
| metadata.dc.url.externa: | https://iovs.arvojournals.org/article.aspx?articleid=2513119&resultClick=1 |
| metadata.dc.relation.ispartof: | Investigative Ophthalmology & Visual Science |
| Aparece nas coleções: | Artigo de Periódico |
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| Arquivo | Descrição | Tamanho | Formato | |
|---|---|---|---|---|
| Anti-Inflammatory Effect of Dexamethasone Controlled.pdf | 956.09 kB | Adobe PDF | Visualizar/Abrir |
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