The dexamethasone nanowafer: A novel method of drug delivery for dry eye disease

September 1, 2015

This review presents a therapeutic nanowafer as an alternative to eye drops for dry eye disease, designed to enhance efficacy and improve patient compliance to treatment. In an experimental animal study, the novel dexamethasone nanowafer drug delivery system was comparable in efficacy to twice-daily dexamethasone eye drop treatment and has the potential to minimise risk of cataract formation and glaucoma.

Take-home message: This review presents a therapeutic nanowafer as an alternative to eye drops for dry eye disease, designed to enhance efficacy and improve patient compliance to treatment. In an experimental animal study, the novel dexamethasone nanowafer drug delivery system was comparable in efficacy to twice-daily dexamethasone eye drop treatment and has the potential to minimise risk of cataract formation and glaucoma.

 

By Dr Ghanashyam Acharya, PhD

Dry eye affects millions of people worldwide and is fast becoming a major public health problem.1,2 Dry eye has a number of causes, including ocular inflammation, hormonal imbalance and aging. Increasing use of visual displays in computers and mobile devices, contact lenses and LASIK surgery can further deteriorate the dry eye condition.3-6  

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Presently, mild dry eye is treated with artificial tear eye drop to hydrate the ocular surface. Such artificial tears provide temporary relief for the patient. Chronic dry eye, which is associated with ocular inflammation, is treated with topical anti-inflammatory corticosteroid or cyclosporine-A eye drops. Although eye drops provide the simplest mode of treatment, therapeutic efficacy and patient compliance are far less than optimal, which is primarily due to rapid clearance of the eye drops by reflex tearing, blinking and nasolacrimal drainage.7,8 Although nanoparticle ophthalmic formulations and drug-loaded contact lenses have been developed to treat dry eye, their efficacy in delivering therapeutically effective drug concentrations to tissues in the anterior segment of the eye, such as cornea and conjunctiva, remains very inefficient.9-11 Together, these limitations have created an unmet need for the development of a drug deliver system that boasts extended release attributes along with an enhanced efficacy to treat dry eye disease.

A novel method of drug delivery

To enhance therapeutic efficacy and improve the patient compliance, a novel nanowafer drug delivery system, the dexamethasone-nanowafer (Dex-NW), has been developed and tested in an experimental mouse dry eye model.12 Designed to restore corneal smoothness and barrier function via the slow release of dexamethasone, the nanowafer is a tiny disc-like membrane that contains drug-loaded nano-reservoirs. It is simply applied on the ocular surface using the fingertips, like a contact lens. During the course of the drug release, the nanowafer dissolves completely.

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In the experimental mouse-model study, hydrogel-forming carboxymethyl cellulose (CMC) polymer was chosen for the nanowafer fabrication. This material was deemed the best choice due to its water solubility, mucoadhesiveness, and current clinical use as an active ingredient in artificial tear eye drops.13,14

Next: Study outcome measurements

 

Study outcome measurements

As part of the study, female mice with induced dry-eye were treated with either one nanowafer containing 10 μg of dexamethasone, which was placed on inferior bulbar conjunctiva, or 2 μL eye drops (containing 10 μg of Dex in 2 μL of 0.1% CMC solution). A group of age- and gender-matched mice that were housed in normal environmental conditions were used as controls.

Evaluation of corneal smoothness

Reflected images of a white ring from the fibre-optic ring illuminator of the stereoscopic zoom microscope (SMZ 1500; Nikon) were obtained immediately after mouse euthanasia. The viewing area was evenly illuminated and nearly shadowless and the regularity of the reflected ring light depended upon the smoothness of the ocular surface.15-17

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Corneal barrier function measurement

Corneal staining was measured by instilling 0.5 μL of Oregon Green Dextran (OGD) on the cornea of both eyes. Digital images were captured and mean fluorescence intensity within a 2mm central corneal ring was measured with NIS Elements (Nikon).

An effective dry eye treatment option

Despite advances in the therapy of dry eye disease, delivering optimum therapeutic drug doses conveniently remains a challenge. The Dex-NW was able to enhance diffusion of a corticosteroid into the cornea and maintain a smooth, healthy corneal surface with intact barrier function in mice with experimentally induced dry eye. Treatment was well tolerated on the mouse eye. In addition, the Dex-NW was effective in suppressing expression of inflammatory mediators associated with corneal dryness.

Next: Final thoughts

 

Twice-daily administration of Dex-NW over five days had the equivalent efficacy of twice-daily topical administration of dexamethasone eye drops during same treatment period. Of course, a more infrequent dosing schedule improves treatment convenience and will likely increase patient compliance. Furthermore, dexamethasone release from the nanowafer can be adjusted to the minimal effective concentration, which, in turn, minimises drug-related toxicity of corticosteroids that can cause glaucoma and cataract formation at higher concentration; a phenomenon often observed with dexamethasone eye drop treatments.

Decording corneal scares straight to 20/20

In summation, the nanowafer drug delivery system holds the therapeutic efficacy and translational potential to treat dry eye disease. Upon further development, Dex-NW can provide a simple and effective treatment with a more convenient dosing schedule than eye drops for dry eye disease.

References

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  • A. Tomlinson. Epidemiology of dry eye disease, in: P.A. Asbell, M.A. Lemp (Eds), Dry Eye Disease: The Clinician's Guide to Diagnosis and Treatment, Thieme Medical Publishers, Inc., New York, 2006, pp. 1-15.

  • The epidemiology of dry eye disease. Report of the Epidemiology Subcommittee of the International Dry Eye Work Shop. Ocul. Surf. 2007;5:93-107.

  • A.J. Bron. Surv. Ophthalmol. 2001;45(Suppl. 2):S221-226.

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  • I.M. Carvalho et al., J. Control. Release. 2015;202:76-82.

  • K. Singh et al., J. Basic Clin. Pharm. 2011;2:87-101.

  • T.G. Coursey et al., J. Control. Release. 2015;213:168–174.

  • M. Moshirfar et al., Clin. Ophthalmol. 2014;8:1419-1433.

  • A. Ludwig. Adv. Drug Deliv. Rev. 2005;57:1595-1639.

  • C.S. De Paiva et al., Invest. Ophthalmol. Vis. Sci. 2006;47:2847-2856.

  • R.M. Corrales et al., Invest. Ophthalmol. Vis. Sci. 2006;47:3293-3302.

  • C.S. De Paiva et al., Arch. Ophthalmology. 2009;127:1625-1631.

 

Dr Ghanashyam Acharya, PhD.

E: gacharya@bcm.edu

Dr Acharya is an Assistant Professor at the Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA.

The author declares no conflicts of interest relating to the content of this article.

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