Anti-Inflammatory Effect of Dexamethasone Controlled Released From Anterior Suprachoroidal Polyurethane Implants on Endotoxin-Induced Uveitis in Rats.

Détails

Ressource 1Télécharger: i1552-5783-57-4-1671 (1).pdf (933.87 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_1B68BE097B7D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Anti-Inflammatory Effect of Dexamethasone Controlled Released From Anterior Suprachoroidal Polyurethane Implants on Endotoxin-Induced Uveitis in Rats.
Périodique
Investigative ophthalmology & visual science
Auteur(s)
Barbosa Saliba J., Vieira L., Fernandes-Cunha G.M., Rodrigues Da Silva G., Ligório Fialho S., Silva-Cunha A., Bousquet E., Naud M.C., Ayres E., Oréfice R.L., Tekaya M., Kowalczuk L., Zhao M., Behar-Cohen F.
ISSN
1552-5783 (Electronic)
ISSN-L
0146-0404
Statut éditorial
Publié
Date de publication
04/2016
Peer-reviewed
Oui
Volume
57
Numéro
4
Pages
1671-1679
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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).
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 ARPE-19 cells using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) test. Short-term 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.
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-1β, 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.
Dexamethasone-PUD implanted in the anterior suprachoroidal space may be of interest in the treatment of intraocular inflammation.

Mots-clé
Animals, Anti-Inflammatory Agents/administration & dosage, Anti-Inflammatory Agents/pharmacokinetics, Cell Line, Cell Survival, Ciliary Body/metabolism, Coloring Agents/pharmacology, Cytokines/genetics, Cytokines/metabolism, Dexamethasone/administration & dosage, Dexamethasone/pharmacokinetics, Disease Models, Animal, Drug Delivery Systems, Drug Implants, Extracellular Space, Female, Humans, Iris/metabolism, Lipopolysaccharides/toxicity, Polyurethanes, Rats, Rats, Inbred Lew, Retinal Pigment Epithelium/drug effects, Salmonella typhimurium, Spectroscopy, Fourier Transform Infrared, Tetrazolium Salts/pharmacology, Thiazoles/pharmacology, Uveitis/chemically induced, Uveitis/metabolism, Uveitis/prevention & control
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/02/2017 8:36
Dernière modification de la notice
20/08/2019 12:52
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