title: 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.affiliation: Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, United States.
authors.forename: Terry G
authors.initials: TG
authors.lastname: Coursey
authors.affiliation: Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, United States.
authors.forename: Johanna Tukler
authors.initials: JT
authors.lastname: Henriksson
authors.affiliation: Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, United States.
authors.forename: Daniela C
authors.initials: DC
authors.lastname: Marcano
authors.affiliation: Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, United States.
authors.forename: Crystal S
authors.initials: CS
authors.lastname: Shin
authors.affiliation: Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, United States.
authors.forename: Lucas C
authors.initials: LC
authors.lastname: Isenhart
authors.affiliation: Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, United States.
authors.forename: Faheem
authors.initials: F
authors.lastname: Ahmed
authors.affiliation: Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, United States.
authors.forename: Cintia S
authors.initials: CS
authors.lastname: De Paiva
authors.affiliation: Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, United States.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Pflugfelder
authors.affiliation: Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, United States. Electronic address: gacharya@bcm.edu.
authors.forename: Ghanashyam
authors.initials: G
authors.lastname: Acharya
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry*; D003315:Cornea / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D003692:Delayed-Action Preparations / Q000737:chemistry*; D003907:Dexamethasone / Q000008:administration & dosage* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D015352:Dry Eye Syndromes / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D003692:Delayed-Action Preparations; D003907:Dexamethasone; D002266:Carboxymethylcellulose Sodium
keywords: Cornea; Dexamethasone; Drug delivery; Dry eye; Inflammation; Nanowafer