Sustained treatment of retinal vascular diseases with self-aggregating sunitinib microparticles
Open Access
- 4 February 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 11 (1), 1-13
- https://doi.org/10.1038/s41467-020-14340-x
Abstract
Neovascular age-related macular degeneration and diabetic retinopathy are prevalent causes of vision loss requiring frequent intravitreous injections of VEGF-neutralizing proteins, and under-treatment is common and problematic. Here we report incorporation of sunitinib, a tyrosine kinase inhibitor that blocks VEGF receptors, into a non-inflammatory biodegradable polymer to generate sunitinib microparticles specially formulated to self-aggregate into a depot. A single intravitreous injection of sunitinib microparticles potently suppresses choroidal neovascularization in mice for six months and in another model, blocks VEGF-induced leukostasis and retinal nonperfusion, which are associated with diabetic retinopathy progression. After intravitreous injection in rabbits, sunitinib microparticles self-aggregate into a depot that remains localized and maintains therapeutic levels of sunitinib in retinal pigmented epithelium/choroid and retina for more than six months. There is no intraocular inflammation or retinal toxicity. Intravitreous injection of sunitinib microparticles provides a promising approach to achieve sustained suppression of VEGF signaling and improve outcomes in patients with retinal vascular diseases. Neovascular age-related macular degeneration and diabetic retinopathy are currently treated with repeated intravitreous injections of VEGF neutralizing proteins. Here the authors develop a microparticle-loaded tyrosine kinase inhibitor therapy, which is effective for six months after a single injection in preclinical models.Funding Information
- Research to Prevent Blindness (none)
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