Sustained treatment of retinal vascular diseases with self-aggregating sunitinib microparticles

• DOI: 10.1038/s41467-020-14340-x
• Publication Date: 2020-02-04T11:02:47Z
• Authors: Hiroki Tsujinaka; Jie Fu; Jikui Shen; Yun Yu; Zibran Hafiz; Joshua Kays; David McKenzie; Delia Cardona; David Culp; Ward Peterson; Brian C. Gilger; Christopher S. Crean; Jin-Zhong Zhang; Yogita Kanan; Weiling Yu; Jeffrey L. Cleland; Ming Yang; Justin Hanes; Peter A. Campochiaro
• Keywords: Male; Vascular Endothelial Growth Factor A; 0301 basic medicine; Swine; Science; Q; Article; Choroidal Neovascularization; 3. Good health; 12. Responsible consumption; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Receptors, Vascular Endothelial Growth Factor; Retinal Diseases; Sunitinib; Animals; Humans; Swine, Miniature; Female; Rabbits

Abstract Neovascular age-related macular degeneration and diabetic retinopathy are prevalent causes of vision loss requiring frequent intravitreous injections VEGF-neutralizing proteins, under-treatment is common problematic. Here we report incorporation sunitinib, a tyrosine kinase inhibitor that blocks VEGF receptors, into non-inflammatory biodegradable polymer to generate sunitinib microparticles specially formulated self-aggregate depot. A single injection potently suppresses choroidal neovascularization in mice for six months another model, VEGF-induced leukostasis retinal nonperfusion, which associated with progression. After rabbits, depot remains localized maintains therapeutic levels pigmented epithelium/choroid retina more than months. There no intraocular inflammation or toxicity. Intravitreous provides promising approach achieve sustained suppression signaling improve outcomes patients vascular diseases.