September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
ROS-responsive nanoparticles to extend the lifetime of anti-angiogenic drugs
Author Affiliations & Notes
  • Viet Anh Nguyen Huu
    Nanoengineering & School of Pharmacy, University of California, San Diego, La Jolla, California, United States
  • Jie Zhu
    School of Medicine, University of California, San Diego, La Jolla, California, United States
  • Jing Luo
    School of Medicine, University of California, San Diego, La Jolla, California, United States
  • Sherrina Patel
    School of Medicine, University of California, San Diego, La Jolla, California, United States
  • Guillaume Collet
    School of Pharmacy, University of California, San Diego, La Jolla, California, United States
  • Caroline de Gracia Lux
    School of Pharmacy, University of California, San Diego, La Jolla, California, United States
  • Kang Zhang
    School of Medicine, University of California, San Diego, La Jolla, California, United States
  • Adah Almutairi
    School of Pharmacy, University of California, San Diego, La Jolla, California, United States
  • Footnotes
    Commercial Relationships   Viet Anh Nguyen Huu, None; Jie Zhu, None; Jing Luo, None; Sherrina Patel, None; Guillaume Collet, None; Caroline de Gracia Lux, None; Kang Zhang, None; Adah Almutairi, None
  • Footnotes
    Support  P30EY022589
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3328. doi:
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    • Get Citation

      Viet Anh Nguyen Huu, Jie Zhu, Jing Luo, Sherrina Patel, Guillaume Collet, Caroline de Gracia Lux, Kang Zhang, Adah Almutairi; ROS-responsive nanoparticles to extend the lifetime of anti-angiogenic drugs. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3328.

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

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Abstract

Purpose : Treatment of macular degeneration and proliferative diabetic retinopathy with anti-angiogenic drugs currently requires repeated injections. As the pathophysiology of these diseases involves oxidative stress (ROS), we are examining whether delivering VEGF-Trap in nanoparticles that degrade and release cargo in response to reactive oxygen species lengthen its lifetime in the eye. This approach should tailor the amount of drug released to the progression of the disease.

Methods : The efficacy and pharmacokinetics of VEGF-Trap in the following formulations are being compared in mice with oxygen-induced retinopathy (OIR) and with laser-induced choroidal neovascularization (CNV): in ROS-responsive particles (composed of a polyester bearing boronic ester groups), in slowly-degrading particles (poly(lactic-co-glycolic acid) (PLGA)), and free drug. Efficacy is measured by lectin staining and fluorescein angiography. To assess lifetime, we examine whether VEGF-Trap delivered up to three months prior to laser induction protects against CNV.

Results : ROS-responsive particles are compatible with intravitreal administration, as they have no effect on electroretinography, intraocular pressure, or expression of inflammatory cytokines. VEGF-Trap is effective in preventing neovascularization in OIR when administered as a free drug (40 µg) or in ROS-responsive particles, but not in PLGA. ROS-responsive particles are also effectively releasing VEGF-Trap that inhibits choroidal neovascularization in animals injected three months prior to the insult.

Conclusions : VEGF-Trap retains activity upon formulation in particles by nanoemulsion. ROS-responsive particles allow greater release of VEGF-Trap in eyes affected by neovascularization than PLGA particles, suggesting potential for use in formulation of anti-angiogenics.

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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