title: Ocular drug delivery nanowafer with enhanced therapeutic efficacy.
abstract: Presently, eye injuries are treated by topical eye drop therapy. Because of the ocular surface barriers, topical eye drops must be applied several times in a day, causing side effects such as glaucoma, cataract, and poor patient compliance. This article presents the development of a nanowafer drug delivery system in which the polymer and the drug work synergistically to elicit an enhanced therapeutic efficacy with negligible adverse immune responses. The nanowafer is a small transparent circular disc that contains arrays of drug-loaded nanoreservoirs. The slow drug release from the nanowafer increases the drug residence time on the ocular surface and its subsequent absorption into the surrounding ocular tissue. At the end of the stipulated period of drug release, the nanowafer will dissolve and fade away. The in vivo efficacy of the axitinib-loaded nanowafer was demonstrated in treating corneal neovascularization (CNV) in a murine ocular burn model. The laser scanning confocal imaging and RT-PCR study revealed that once a day administered axitinib nanowafer was therapeutically twice as effective, compared to axitinib delivered twice a day by topical eye drop therapy. The axitinib nanowafer is nontoxic and did not affect the wound healing and epithelial recovery of the ocular burn induced corneas. These results confirmed that drug release from the axitinib nanowafer is more effective in inhibiting CNV compared to the topical eye drop treatment even at a lower dosing frequency.
authors.affiliation: Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine , One Baylor Plaza, Houston, Texas 77030, United States.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Yuan
authors.forename: Daniela C
authors.initials: DC
authors.lastname: Marcano
authors.forename: Crystal S
authors.initials: CS
authors.lastname: Shin
authors.forename: Xia
authors.initials: X
authors.lastname: Hua
authors.forename: Lucas C
authors.initials: LC
authors.lastname: Isenhart
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Pflugfelder
authors.forename: Ghanashyam
authors.initials: G
authors.lastname: Acharya
mesh_terms: D000818:Animals; D000077784:Axitinib; D003315:Cornea / Q000098:blood supply / Q000187:drug effects / Q000276:immunology; D016510:Corneal Neovascularization / Q000188:drug therapy; D004058:Diffusion; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D005123:Eye / Q000098:blood supply / Q000187:drug effects / Q000276:immunology; D005260:Female; D007093:Imidazoles / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D007191:Indazoles / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D036103:Nanotechnology / Q000379:methods*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D014945:Wound Healing / Q000187:drug effects
chemical_list: D007093:Imidazoles; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D000077784:Axitinib; D020794:Receptor Protein-Tyrosine Kinases
keywords: corneal neovascularization; drug delivery; inflammation; nanowafer; therapeutic efficacy