September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Sustained suppression of murine choroidal neovascularization by intravitreous injection of sunitinib-encapsulated polymer microparticles.
Author Affiliations & Notes
  • Raquel Formica
    Ophthalmology, Johns Hopkins University Wilmer Eye Institure, Baltimore, Maryland, United States
  • Jie Fu
    Ophthalmology, Johns Hopkins University Wilmer Eye Institure, Baltimore, Maryland, United States
  • Ji-kui Shen
    Ophthalmology, Johns Hopkins University Wilmer Eye Institure, Baltimore, Maryland, United States
  • Ming Yang
    Graybug, Inc., Baltimore, Maryland, United States
  • Yun Yu
    Graybug, Inc., Baltimore, Maryland, United States
  • Joshua Kays
    Graybug, Inc., Baltimore, Maryland, United States
  • Yanfei Liu
    Ophthalmology, Johns Hopkins University Wilmer Eye Institure, Baltimore, Maryland, United States
  • Ward M Peterson
    Graybug, Inc., Baltimore, Maryland, United States
  • Jeffrey Cleland
    Graybug, Inc., Baltimore, Maryland, United States
  • Justin Hanes
    Ophthalmology, Johns Hopkins University Wilmer Eye Institure, Baltimore, Maryland, United States
  • Peter A Campochiaro
    Ophthalmology, Johns Hopkins University Wilmer Eye Institure, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Raquel Formica, None; Jie Fu, None; Ji-kui Shen, None; Ming Yang, Graybug, Inc (E); Yun Yu, Graybug, Inc (E); Joshua Kays, Graybug, Inc (E); Yanfei Liu, None; Ward Peterson, Graybug, Inc (E); Jeffrey Cleland, Graybug, Inc (E); Justin Hanes, Graybug, Inc (I); Peter Campochiaro, Graybug, Inc (I)
  • Footnotes
    Support  SBIR Grant R43EY024827
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2147. doi:
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      Raquel Formica, Jie Fu, Ji-kui Shen, Ming Yang, Yun Yu, Joshua Kays, Yanfei Liu, Ward M Peterson, Jeffrey Cleland, Justin Hanes, Peter A Campochiaro; Sustained suppression of murine choroidal neovascularization by intravitreous injection of sunitinib-encapsulated polymer microparticles.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2147.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To evaluate the long-term efficacy of sunitinib released from biodegradable polymer microparticles following intravitreous (IVT) injection in a mouse model of laser-induced choroidal neovascularization (CNV).

Methods : Biodegradable polymer microparticles were prepared for sustained delivery of sunitinib, an FDA-approved potent receptor tyrosine kinase inhibitor that blocks all members of the VEGF and PDGF receptor families. Microparticles were characterized in vitro, including average size, size distribution, drug loading, and drug release profile. Cohorts of C57BL/6 mice (n=5) had IVT injection of sunitinib microparticles (10 µg total drug content) and laser-induced rupture of Bruch’s membrane at 0, 2, 4, or 8 weeks after injection. The area of CNV was measured one week after laser treatment (1, 3, 5, and 9 weeks after microparticle injection). A pharmacokinetic study was also conducted using normal C57BL/6 mice and the drug levels in different ocular tissues were determined by HPLC-MS at various time points following IVT injection of the microparticles.

Results : The microparticles had drug loading of 3.4% (by weight) and a mean diameter of about 13 µm. A statistically significant reduction in the area of CNV was observed at each time point through 9 weeks in microparticle-injected eyes compared with corresponding controls. The mean area of CNV (mm2 x 10-3) in microparticle-injected eyes versus controls was: 1 week, 5.0±0.9 vs 8.0±1.0; 3 weeks, 10.6±1.2 vs 15.3±1.5; 5 weeks, 8.6±1.5 vs 14.5±1.7; and 9 weeks, 9.7±3.7 vs 22.5±5.4.

Conclusions : IVT injection of sunitinib microparticles provides sustained suppression of CNV and may provide a durable new treatment for neovascular AMD.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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