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

Abstract

PurposeTo evaluate the efficacy of a controlled release dexamethasone delivery system for suppressing inflammation in an ocular burn + desiccating stress (OB+DS) model.MethodsNanowafers (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.ResultsBoth 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.ConclusionsDex-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.

Ocular Drug Delivery: Present Innovations and Future Challenges

“…This novel nanocarrier is designed from biodegradable and biocompatible polymers which can be eliminated over a period of time. Coursey et al (2015) and Bian et al (2016) developed a dexamethasone-loaded nanowafer (Dex-NW) for the treatment of dry eye disease. The nanowafer was fabricated using carboxymethyl cellulose polymer and consisted of an array of nano drug reservoirs filled with dexamethasone.…”

“…Yet another interesting finding the scientists reported was that Dex-NW was effective in lowering the overexpression of inflammatory cytokines such as tumor necrosis factor-a, interferon-g, interleukin-1b, and interleukin-6. Also, the expression of inflammatory chemokines such as CXCL-10, CCL-5, and MMP-3 and MMP-9 was lowered (Coursey et al, 2015;Bian et al, 2016). Axitinibloaded nanowafers were developed by Yuan et al for the treatment of CNV (Yuan et al, 2015).…”

Ocular delivery of proteins and peptides: Challenges and novel formulation approaches

“…The same group reported the efficacy of such PVA fabricated nanowafer loaded with axitinib for treating CNV in a murine ocular burn model [196, 197]. This smart platform integrating nanofabrication as well as drug delivery technologies has been able to establish itself further by demonstrating sustained delivery of dexamethasone and cysteamine for effective treatment of dry eye disease and corneal cystinosis respectively [198–200]. These results provide a strong rationale for their translation and clinical application in biopharmaceuticals delivery.…”

Matrix metalloproteinase-9 in the pathophysiology and diagnosis of dry eye syndrome

“…[82][83][84][85] This simulated the most severe burn cases, where extensive facial and eyelid thermal injury results in eye exposure and desiccation due to loss of protection from the eyelids and reduced blinking. We found there was an additive pathogenic effect of dry eye to alkali burn, with amplification of MMP-3, -8, -9 and -12, IL-6 and IL-1β mRNA expression and sterile corneal perforation in ~30% of animals subjected to the chemical burn and desiccating conditions.…”