Nine-million Americans suffer progressive vision loss due to retinal neurodegenerative diseases such as age-related macular degeneration or retinitis pigmentosa. An emerging body of literature has identified that retinal neuroinflammation plays a key role in the pathogenesis of photoreceptor and retinal pigment epithelial cell loss in these diseases. Implants for sustained intravitreal delivery of Fluocinolone Acetonide (FA) have been developed and are FDA-approved for use in patients with uveitis. Even though effective, these devices are non-erodible and surgically implanted, with side effects arising from multiple incisional procedures and a high (>50%) incidence of glaucoma. There is a need to safely deliver these highly effective neuroprotective steroids over a sustained period. Our goal is to address this by developing dendrimer-based nanoscale ocular drug delivery systems that can preferentially suppress retinal neuroinflammation. Dendritic polymers (size ~5 nm) are emerging as a new class of nanoscale drug delivery vehicles, because of their well-defined structure, tailorable surface properties, and the ability to deliver drugs intracellularly. We are developing injectible drug-delivery platforms, by employing dendrimer-drug nanodevices. We will present results on the ocular biodistribution of fluorescently-labeled dendrimers, and the in vivo evaluation of their efficacy over a six month period.

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