Dexamethasone Drug Eluting Nanowafers Control Inflammation in Alkali-Burned Corneas Associated With Dry Eye

• Published in: Investigative ophthalmology & visual science 2016-06, Vol.57 (7), p.3222-3230
• Main Authors: Bian, Fang, Shin, Crystal S, Wang, Changjun, Pflugfelder, Stephen C, Acharya, Ghanashyam, De Paiva, Cintia S
• Format: Article
• Language: English
• Subjects: Alkalies - toxicity; Animals; Burns, Chemical - complications; Burns, Chemical - drug therapy; Burns, Chemical - pathology; Cornea - drug effects; Cornea - pathology; Delayed-Action Preparations; Dexamethasone - administration & dosage; Disease Models, Animal; Drug Delivery Systems; Dry Eye Syndromes - drug therapy; Dry Eye Syndromes - etiology; Dry Eye Syndromes - pathology; Eye Burns - complications; Eye Burns - drug therapy; Eye Burns - pathology; Female; Glucocorticoids - administration & dosage; Mice; Mice, Inbred C57BL; Nanostructures; Nanotechnology and Regenerative Medicine
• ISSN: 1552-5783; 0146-0404; 1552-5783
• DOI: 10.1167/iovs.16-19074

To evaluate the efficacy of a controlled release dexamethasone delivery system for suppressing inflammation in an ocular burn + desiccating stress (OB+DS) model. Nanowafers (NW) loaded with Dexamethasone (Dex, 10 μg) or vehicles (2.5% Methylcellulose; MC) were fabricated using hydrogel template strategy. C57BL/6 mice were subjected to unilateral alkali ocular burn with concomitant desiccating stress for 2 or 5 days and topically treated either with 2 μL of 0.1% Dex or vehicle four times per day and compared with mice that had MC-NW or Dex-NW placed on their corneas. Clinical parameters were evaluated daily. Mice were euthanized after 2 or 5 days. Quantitative PCR evaluated the expression of inflammatory cytokines IL-1β and IL-6 and matrix metalloproteinases (MMP) in whole cornea lysates. Myeloperoxidase activity (MPO) was measured using a commercial kit in cornea lysates. Both Dex drop and Dex-NW groups had significantly lower corneal opacity scores compared with their vehicles. Both Dex drops and Dex-NW significantly decreased expression of IL-1β, IL-6, and MMP-9 RNA transcripts compared with vehicle drops or wafers 2 and 5 days after the initial lesion. A significant lower number of neutrophils was found in both Dex treatment groups and this was accompanied by decreased MPO activity compared with vehicle controls. Dex-NW has efficacy equal to Dex drops in preserving corneal clarity and decreasing expression of MMPs and inflammatory cytokines of the corneas of mice subjected to an OB+DS model.