title: Topical delivery of a Rho-kinase inhibitor to the cornea via mucoadhesive film.
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.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, Wales, UK.
authors.forename: Wendy
authors.initials: W
authors.lastname: Chan
authors.affiliation: School of Optometry & Vision Sciences, Cardiff University, Maindy Road, Cardiff, CF24 4HQ, Wales, UK.
authors.forename: Alina
authors.initials: A
authors.lastname: Akhbanbetova
authors.affiliation: School of Optometry & Vision Sciences, Cardiff University, Maindy Road, Cardiff, CF24 4HQ, Wales, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Quantock
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, Wales, UK. Electronic address: heard@cardiff.ac.uk.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Heard
mesh_terms: D000268:Adhesiveness; D000287:Administration, Topical; D000577:Amides / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D003315:Cornea / Q000378:metabolism*; D004058:Diffusion; D016503:Drug Delivery Systems; D065546:Drug Liberation; D008751:Methylene Blue / Q000008:administration & dosage / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D011725:Pyridines / Q000008:administration & dosage* / Q000737:chemistry; D013552:Swine; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000577:Amides; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C108830:Y 27632; D054460:rho-Associated Kinases; D008751:Methylene Blue
keywords: Cornea; Cryoprobe; Diffusional release; Mucadhesive film; Ocular delivery; ROCK inhibitor; Topical delivery