Dexamethasone nanowafer as an effective therapy for dry eye disease.

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.

• Authors: Terry G Coursey, Johanna Tukler Henriksson, Daniela C Marcano, Crystal S Shin, Lucas C Isenhart, Faheem Ahmed, Cintia S De Paiva, Stephen C Pflugfelder, Ghanashyam Acharya
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 213 Pg. 168-174 (Sep 10 2015) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 26184051 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

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

Topics

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