Age-related macular degeneration (AMD) is one of the leading causes of blindness in adults over the age of 60. Currently, at least 11 million patients in the United States have some form of macular degeneration and this number is projected to grow as the population ages. The more severe form of the disease – neovascular (wet) AMD, is characterized by intraocular neovascularization, inflammation, and retinal damage; however, the disease progression can be deterred through intraocular injections of anti-angiogenic agents. The complications and burden that arise from repetitive injections as well as the difficulty posed by targeting the posterior segment of the eye make this an interesting territory for the development of novel drug delivery systems. New methods for drug delivery are being investigated exploring the use of nanoparticles and other polymeric materials. The goal of this project is to study the potential use of poly(lactide-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles in thermoreversible gels as localized sustained intraocular drug delivery. We prepared stable and reproducible corticosteroid-encapsulated nanoparticles in thermoreversible gels to inhibit vascular endothelial growth factor (VEGF) overexpression characteristic of neovascular AMD. We characterized the drug delivery system by obtaining size, shape, and drug encapsulation data. We also demonstrated that the polymer could be injected into the vitreous as a solution and transition to a gel phase based on the temperature difference between regular indoor environment and the vitreous body. The drug delivery system was tested on human retinal pigment epithelial cells (ARPE-19), for cytotoxicity, uptake and VEGF expression. We also examined the drug delivery system's ability to mitigate the disease progression in a mouse model of choroidal neovascularization (CNV). The effect on blood vessel area was shown and the changes in the mRNA expression of angiogenesis mediators were analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR). These results indicate that the proposed drug delivery systems has the promise to be developed for retinal diseases, involving CNV, including neovascular AMD. Further studies are warranted in developing this promising intraocular drug delivery system for wet AMD and similar ophthalmic diseases. / Ph. D.

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<p>The use of silicon nanoneedles provides a unique and versatile biointerface for a range of biomedical applications. In this work, we propose a rational design for vertical Si nanoneedles that are printed on a polymer substrate for ocular drug delivery, intracellular recording, and intra-organoid sensing. To enable minimally invasive and long-term sustained delivery of ocular drugs, we integrate vertical Si nanoneedles with a tear-soluble contact lens for ocular drug delivery. We demonstrate the effectiveness of this platform in treating corneal neovascularization in an in vivo rabbit model, surpassing the current gold standard surgical therapy. This platform has the potential to revolutionize the management of various chronic ocular diseases without causing significant side effects.</p> <p>To enable intracellular recording, we present a unique platform consisting of vertical Si nanoneedles coated with a thin, transparent network of Au-Ag nanowires. This platform is held in place and enclosed by a soft, transparent elastomer, providing simultaneous intracellular recording and live imaging with applications in neuroscience, cardiology, muscle physiology, and drug screening. To demonstrate the utility of this platform, we monitored electrical potentials from cardiomyocyte cells and cardiovascular organoids. Additionally, we propose an intra-organoid sensing platform with vertical Si nanoneedles transfer printed into a soft scaffold. This platform can be adjusted and tailored for various organoids and tumor tissues of interest, or used to deliver bioactive molecules of interest into organoids in response to external stimuli.</p> <p>Our proposed designs of vertical Si nanoneedles based platforms demonstrate their significant potential for a broad range of biomedical applications, including ocular drug delivery, intracellular recording, and intraorganoid sensing. These platforms have the potential to revolutionize current approaches and pave the way for future developments in biomedical research and clinical applications, offering new possibilities for the diagnosis and treatment of a wide range of diseases.</p>