Dexamethasone Drug Eluting Nanowafers Control Inflammation in Alkali-Burned Corneas Associated With Dry Eye.
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.
Fang
F
Bian
Crystal S
CS
Shin
Changjun
C
Wang
Stephen C
SC
Pflugfelder
Ghanashyam
G
Acharya
Cintia S
CS
De Paiva
D000468:Alkalies / Q000633:toxicity; D000818:Animals; D002057:Burns, Chemical / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D003315:Cornea / Q000187:drug effects / Q000473:pathology; D003692:Delayed-Action Preparations; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D015352:Dry Eye Syndromes / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D005126:Eye Burns / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D049329:Nanostructures
D000468:Alkalies; D003692:Delayed-Action Preparations; D005938:Glucocorticoids; D003907:Dexamethasone