Biocompatibility of thermo-responsive hydrogel ocular drug delivery system

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DESCRIPTION (provided by applicant): Recently employed anti-vascular endothelial growth factor (VEGF) therapy is a very promising treatment for the wet form of age-related macular degeneration and diabetic retinopathy. To be effective, multiple intravitreal injections are needed every four to six weeks. This is not a desirable method as it is associated with several inherent complications. Currently, there is no alternative method; hence, there is a great need to develop a relatively non-invasive delivery method that is more effective than the current clinical regimen. The proposed drug delivery system uses thermo-responsive hydrogel that would optimize the anti-angiogenic effects but minimize the potential for ectopic effects of a large bolus delivery. Due to its novel thermo-responsive characteristic, the hydrogel can be injected as a liquid form to the juxtascleral region or vitreous cavity via a small gauge needle. Once exposed to the body temperature, the solution will become a solid gel that will release the anti-VEGF agents. In vitro studies have demonstrated that thermo-responsive hydrogels can encapsulate and release active protein. The goal of this proposal is to investigate the feasibility and biocompatibility of thermo-responsive hydrogel as an ocular drug delivery system in vivo. Specific Aim 1 will investigate the biocompatibility of the thermo-responsive implant in either the vitreous cavity or juxtascleral region in an in vivo rodent model. To evaluate biocompatibility, electroretinogram (ERG) responses, scanning laser ophthalmoscope (SLO)-imaging blood flow measurements, spectral domain optical coherence tomography (SD-OCT) imaging and histological examination of retinal toxicity and inflammation will be performed at various time points after the implantation. Specific Aim 2 will determine the efficacy of released anti-VEGF from the hydrogels to suppress angiogenic responses in a laser-induced choroidal neovascularization rodent model. ERG responses, SLO-imaging blood flow measurements, OCT imaging and histology will be used to evaluate the efficacy. Widespread clinical use of anti-VEGF necessitates a practical and effective delivery method to the posterior segment. The innovation of this project is that a novel biomaterial will be used to minimize the need for repeated intravitreal injections and improve the efficacy of the drug. The proposed drug delivery system will have a great impact on the current treatment regimen. PUBLIC HEALTH RELEVANCE: Widespread clinical use of anti-vascular endothelial growth factor (VEGF) therapy necessitates a practical and effective delivery method to the posterior segment of the eye. Recently developed biodegradable thermo- responsive hydrogel system has demonstrated to encapsulate and release active protein. The overall goal of this proposal is to investigate the feasibility and biocompatibility of thermo-responsive hydrogel as an ocular drug delivery system which can have a significant impact on the current treatment of age-related macular degeneration and diabetic retinopathy.