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

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.

• Authors: Fang Bian, Crystal S Shin, Changjun Wang, Stephen C Pflugfelder, Ghanashyam Acharya, Cintia S De Paiva
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 57 Issue 7 Pg. 3222-30 (06 01 2016) ISSN: 1552-5783 [Electronic] United States
• PMID: 27327581 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural)

Chemical References

• Alkalies
• Delayed-Action Preparations
• Glucocorticoids
• Dexamethasone

Topics

• Alkalies (toxicity)
• Animals
• Burns, Chemical (complications, drug therapy, pathology)
• Cornea (drug effects, pathology)
• Delayed-Action Preparations
• Dexamethasone (administration & dosage)
• Disease Models, Animal
• Drug Delivery Systems
• Dry Eye Syndromes (drug therapy, etiology, pathology)
• Eye Burns (complications, drug therapy, pathology)
• Female
• Glucocorticoids (administration & dosage)
• Mice
• Mice, Inbred C57BL
• Nanostructures