Anti-inflammatory effect of dexamethasone controlled released from anterior suprachoroidal polyurethane implants on endotoxin-induced uveitis in rats
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Universidade Federal de Minas Gerais
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Artigo de periódico
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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.
Abstract
Assunto
Implantes de medicamento, Uveíte, Oftalmopatias, Uveíte induzido quimicamente
Palavras-chave
Polyurethane, Implant, Suprachoroidal space, Drug delivery, Endotoxin-induced uveitis
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https://iovs.arvojournals.org/article.aspx?articleid=2513119&resultClick=1