Dexamethasone nanowafer as an effective therapy for dry eye disease

J Control Release. 2015 Sep 10;213:168-174. doi: 10.1016/j.jconrel.2015.07.007. Epub 2015 Jul 13.

Abstract

Dry eye disease is a major public health problem that affects millions of people worldwide. It is presently treated with artificial tear and anti-inflammatory eye drops that are generally administered several times a day and may have limited therapeutic efficacy. To improve convenience and efficacy, a dexamethasone (Dex) loaded nanowafer (Dex-NW) has been developed that can release the drug on the ocular surface for a longer duration of time than drops, during which it slowly dissolves. The Dex-NW was fabricated using carboxymethyl cellulose polymer and contains arrays of 500 nm square drug reservoirs filled with Dex. The in vivo efficacy of the Dex-NW was evaluated using an experimental mouse dry eye model. These studies demonstrated that once a day Dex-NW treatment on alternate days during a five-day treatment period was able to restore a healthy ocular surface and corneal barrier function with comparable efficacy to twice a day topically applied dexamethasone eye drop treatment. The Dex-NW was also very effective in down regulating expression of inflammatory cytokines (TNF-α, and IFN-γ), chemokines (CXCL-10 and CCL-5), and MMP-3, that are stimulated by dry eye. Despite less frequent dosing, the Dex-NW has comparable therapeutic efficacy to topically applied Dex eye drops in experimental mouse dry eye model, and these results provide a strong rationale for translation to human clinical trials for dry eye.

Keywords: Cornea; Dexamethasone; Drug delivery; Dry eye; Inflammation; Nanowafer.

Publication types

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

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / therapeutic use
  • Carboxymethylcellulose Sodium / chemistry*
  • Cornea / drug effects*
  • Cornea / immunology
  • Cornea / pathology
  • Cytokines / immunology
  • Delayed-Action Preparations / chemistry*
  • Dexamethasone / administration & dosage*
  • Dexamethasone / therapeutic use
  • Drug Delivery Systems
  • Dry Eye Syndromes / drug therapy*
  • Dry Eye Syndromes / immunology
  • Dry Eye Syndromes / pathology
  • Female
  • Mice, Inbred C57BL
  • Nanostructures / chemistry

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Delayed-Action Preparations
  • Dexamethasone
  • Carboxymethylcellulose Sodium