June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Biodegradable polymeric microparticles allow sustained durability of a multimodal anti-angiogenic peptide to treat neovascular age-related macular degeneration
Author Affiliations & Notes
  • Jayoung Kim
    Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States
  • Raquel Formica
    Ophthalmology, Johns Hopkins Wilmer Eye Institute, Baltimore, Maryland, United States
  • Ron Shmueli
    Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States
    AsclepiX Therapeutics, Baltimore, Maryland, United States
  • Adam Mirando
    Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States
  • Niranjan B Pandey
    Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States
    AsclepiX Therapeutics, Baltimore, Maryland, United States
  • Aleksander S Popel
    Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States
    AsclepiX Therapeutics, Baltimore, Maryland, United States
  • Peter A Campochiaro
    Ophthalmology, Johns Hopkins Wilmer Eye Institute, Baltimore, Maryland, United States
  • Jordan J Green
    Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States
    AsclepiX Therapeutics, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Jayoung Kim, None; Raquel Formica, None; Ron Shmueli, AsclepiX Therapeutics (E); Adam Mirando, None; Niranjan Pandey, AsclepiX Therapeutics (E); Aleksander Popel, AsclepiX Therapeutics (I), AsclepiX Therapeutics (P), AsclepiX Therapeutics (S), AsclepiX Therapeutics (R); Peter Campochiaro, Aerpio Therapeutics (F), Aerpio Therapeutics (C), Alimera (F), Alimera (C), Allegro (F), Allegro (C), Allegro (I), Applied Genetic Technologies (C), AsclepiX Therapeutics (F), AsclepiX Therapeutics (C), Genentech/Roche (F), Genentech/Roche (C), Genzyme (F), GlaxoSmithKline (F), Graybug (C), Graybug (I), Intrexon (C), Merck (C), Oxford Biomedica (F), Regeneron (F), Regenxbio (F), Regenxbio (C), Rxi (F), Rxi (C); Jordan Green, AsclepiX Therapeutics (I), AsclepiX Therapeutics (P), AsclepiX Therapeutics (S), AsclepiX Therapeutics (R)
  • Footnotes
    Support  NIH grants 1R21EY022986-01,1R43EY024495, and 1R43EY025903.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1949. doi:
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      Jayoung Kim, Raquel Formica, Ron Shmueli, Adam Mirando, Niranjan B Pandey, Aleksander S Popel, Peter A Campochiaro, Jordan J Green; Biodegradable polymeric microparticles allow sustained durability of a multimodal anti-angiogenic peptide to treat neovascular age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1949.

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

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Abstract

Purpose : A novel collagen-derived anti-angiogenic peptide is effective against choroidal neovascularization (CNV) following intravitreal injection in neovascular age-related macular degeneration (NVAMD) models in mice. In order to increase duration of action of the peptide and minimize intravitreal dosing frequency, we report biodegradable polymeric microparticle (MP) delivery systems that encapsulate and protect the biomimetic peptide from degradation, enable controlled release, and demonstrate prolonged therapeutic effect in vivo.

Methods : Three poly(lactide-co-glycolide) PLGA MP formulations with varying polymer hydrophobicity and shape were formulated using a single emulsion method to study the kinetics of peptide release and therapeutic efficacy. For anisotropic ellipsoidal MPs, spherical MPs casted on poly(vinyl alcohol) film were physically stretched at above glass transition temperature. For suppression of CNV, C57BL/6 mice received intravitreal injections for different periods of time prior to laser induction. Mice were sacrificed 2 weeks following laser induction and area of NV was quantified.

Results : 4-5 μm PLGA MPs with 0.5-1% loading of the peptide by mass were injected in mouse vitreous at a 50 μg peptide dosage. While naked peptide showed significant suppression of NV only up to 2 weeks, less hydrophobic PLGA MP (LMP) loaded with the peptide maintained its efficacy of more than 25% suppression up to 8 weeks. More hydrophobic PLGA MP (HMP) further extended the efficacy to 16 weeks and showed 33% suppression in comparison to control eye. Ellipsoidal PLGA MP derived from HMP, which mitigate acute immune response due to their anisotropic shape, also sustained significant NV suppression for an extended period of time to at least 16 weeks (Figure).

Conclusions : Ellipsoidal biodegradable PLGA MPs can successfully deliver anti-angiogenic peptide and prolong its therapeutic effect for at least four months in a murine NVAMD model without any observed visual impairment following a single intravitreal injection. This approach is promising to enhance the durability of a novel biomimetic multimodal anti-angiogenic peptide to treat NVAMD.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

Inhibition of neovasculature over time in a murine laser-induced CNV model following a single intravitreal injection of ellipsoidal PLGA HMPs encapsulating anti-angiogenic peptide.

Inhibition of neovasculature over time in a murine laser-induced CNV model following a single intravitreal injection of ellipsoidal PLGA HMPs encapsulating anti-angiogenic peptide.

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