Abstract
Corneal disease is a leading cause of blindness globally, and is commonly associated with corneal neovascularization, which results in the loss of optical clarity and visual impairment. A wide variety of factors contribute to abnormal growth of new blood vessels into the cornea, including contact lens wear, infectious keratitis, corneal graft rejection, inflammatory disorders and trauma. In each case, proangiogenic factors such as vascular endothelial, platelet-derived, and fibroblast growth factors fuel new blood vessel growth and proliferation. Topical corticosteroids are a front-line treatment for corneal neovascularization, but require patient compliance and long-term use, which can limit efficacy and lead to increased intraocular pressure or cataract development, respectively. There is a need for a simple, effective treatment for corneal neovascularization that improves access and alleviates compliance issues. Here, biodegradable, sunitinib-loaded, nano- and micro-structured thin films were manufactured via electrospinning and applied topically in a rat model of corneal neovascularization. Thin films were characterized for morphology, mechanical and physicochemical properties, and drug release prior to in vivo assessment of biocompatibility and efficacy. Nano-structured thin films demonstrated sustained in vitro release of sunitinib for 30 days, provided sufficient strength for extended topical application, and were biocompatible on rat eyes. Importantly, sunitinib-loaded thin films inhibited corneal neovascularization more significantly than 3x daily sunitinib eye drops, as evidenced by greater reductions in vessel area, length, and vascular endothelial growth factor expression. This sustained drug-delivery platform has potential to provide a safe and effective treatment for ocular surface and corneal disorders.