Abstract
The application of inhibitors of the Rho kinase pathway (ROCK inhibitors) to the surface of the eye in the form of eyedrops has beneficial effects which aid the recovery of diseased or injured endothelial cells that line the inner surface of the cornea. The aim of this study was to test the plausibility of delivering a selective ROCK inhibitor, Y-27632, to the cornea using a thin polymeric film. Mucoadhesive polymeric thin films were prepared incorporating Y-27632 and diffusional release into PBS was determined. Topical ocular delivery from the applied film was investigated using freshly excised porcine eyes and eyedrops of equivalent concentration acted as comparators; after 24h the formulations were removed and the corneas extracted. Drug-loaded thin polymeric films, with high clarity and pliability were produced. ROCK inhibitor Y-27632 was weakly retained within the film, with release attaining equilibrium after 1h. This in turn facilitated its rapid ocular delivery, and an approximately three-fold greater penetration of Y-27632 into cryoprobe-treated corneas was observed from the thin film (p<0.01) compared to eyedrops. These findings support the further development of ROCK inhibitor delivery to the cornea via release from thin mucoadhesive films to treat vision loss cause by corneal endothelial dysfunction.
Highlights
The cornea of the eye, which is just over 0.5 mm thick in humans, owes its transparency to the characteristic spatial arrangement of its constituent collagens and other extracellular matrix components which make up much of its thickness (Knupp et al, 2009; Meek and Knupp, 2015)
In the experiments described here, to test if cryoprobe-treated eyeballs achieved a better ingress of drug, transcorneal freezing was conducted (Fig. 3) by gently touching the tip of a newly designed cryoprobe onto the surface of freshly obtained porcine eyeballs for 3 s, which we have shown to be optimal to produce reliable and reproducible areas of corneal endothelial cell death
This study has compared drug delivery to the cornea achieved via eye drops or release from mucoadhesive thin films
Summary
The cornea of the eye, which is just over 0.5 mm thick in humans, owes its transparency to the characteristic spatial arrangement of its constituent collagens and other extracellular matrix components which make up much of its thickness (Knupp et al, 2009; Meek and Knupp, 2015). If the endothelial cell layer is compromised the cornea swells and becomes oedematous, scatters light and loses its transparency This results in severe vision loss and in most cases the only option is corneal transplant surgery. Corneal endothelial dysfunction occurs because of an inherited disease called Fuch's endothelial corneal dystrophy (FECD) in which corneal endothelial cells deteriorate or are lost over the years. It can occur as a result of accidental damage to the corneal endothelium during cataract surgery to remove or replace the lens of the eye, and this condition is often referred to as bullous keratopathy.
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