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

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 () and Peter A. Campochiaro ()
Additional contact information
Hiroki Tsujinaka: Johns Hopkins University School of Medicine
Jie Fu: Johns Hopkins University School of Medicine
Jikui Shen: Johns Hopkins University School of Medicine
Yun Yu: Graybug Vision, Inc.
Zibran Hafiz: Johns Hopkins University School of Medicine
Joshua Kays: Graybug Vision, Inc.
David McKenzie: Graybug Vision, Inc.
Delia Cardona: Graybug Vision, Inc.
David Culp: Powered Research, LLC, Research Triangle Park
Ward Peterson: Graybug Vision, Inc.
Brian C. Gilger: Powered Research, LLC, Research Triangle Park
Christopher S. Crean: Graybug Vision, Inc.
Jin-Zhong Zhang: Graybug Vision, Inc.
Yogita Kanan: Johns Hopkins University School of Medicine
Weiling Yu: Graybug Vision, Inc.
Jeffrey L. Cleland: Graybug Vision, Inc.
Ming Yang: Graybug Vision, Inc.
Justin Hanes: Johns Hopkins University School of Medicine
Peter A. Campochiaro: Johns Hopkins University School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-14340-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14340-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-14340-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().