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

Invest Ophthalmol Vis Sci. 2016 Jun 1;57(7):3222-30. doi: 10.1167/iovs.16-19074.

Abstract

Purpose: To evaluate the efficacy of a controlled release dexamethasone delivery system for suppressing inflammation in an ocular burn + desiccating stress (OB+DS) model.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • 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

Substances

  • Alkalies
  • Delayed-Action Preparations
  • Glucocorticoids
  • Dexamethasone