September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
A Sustained Release Formulation of Novel Quininib-Hyaluronic Acid microneedles inhibits Angiogenesis and Retinal Vascular Permeability in vivo
Author Affiliations & Notes
  • Orla Majella Galvin
    The Conway Institute, School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
  • Akshay Srivastava
    Centre for Research in Medical Devices, Bioscience Building, National University of Ireland Galway, Galway, Ireland
  • Oliver Carroll
    Centre for Research in Medical Devices, Bioscience Building, National University of Ireland Galway, Galway, Ireland
  • Rajiv Kulkarni
    RenaSci Ltd, Nottingham, United Kingdom
  • Steve Dykes
    RenaSci Ltd, Nottingham, United Kingdom
  • Steve Vickers
    RenaSci Ltd, Nottingham, United Kingdom
  • Keith Dickinson
    RenaSci Ltd, Nottingham, United Kingdom
  • Robert Jones
    RenaSci Ltd, Nottingham, United Kingdom
  • Sharon Cheetham
    RenaSci Ltd, Nottingham, United Kingdom
  • Abhay Pandit
    Centre for Research in Medical Devices, Bioscience Building, National University of Ireland Galway, Galway, Ireland
  • Breandan N Kennedy
    The Conway Institute, School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
  • Footnotes
    Commercial Relationships   Orla Galvin, None; Akshay Srivastava, None; Oliver Carroll, None; Rajiv Kulkarni, None; Steve Dykes, None; Steve Vickers, None; Keith Dickinson, None; Robert Jones, None; Sharon Cheetham, None; Abhay Pandit, None; Breandan Kennedy, University College Dublin (P)
  • Footnotes
    Support  11/TIDA/B2016
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4018. doi:
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    • Get Citation

      Orla Majella Galvin, Akshay Srivastava, Oliver Carroll, Rajiv Kulkarni, Steve Dykes, Steve Vickers, Keith Dickinson, Robert Jones, Sharon Cheetham, Abhay Pandit, Breandan N Kennedy; A Sustained Release Formulation of Novel Quininib-Hyaluronic Acid microneedles inhibits Angiogenesis and Retinal Vascular Permeability in vivo . Invest. Ophthalmol. Vis. Sci. 2016;57(12):4018.

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

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Abstract

Purpose : Pathologic neovascularisation and ocular permeability are hallmarks of proliferative Diabetic Retinopathy and Age-related Macular Degeneration. Current pharmacologic interventions targeting VEGF are effective in only a subset of patients and require multiple intraocular injections associated with iatrogenic infection. Thus, our goal is to develop novel drugs with sustained ocular-release, that are VEGF-independent, anti-angiogenic and reduce permeability. Here, sustained release of quininib from a novel quininib-hyaluronic acid microneedle formulation is determined in vitro, and the safety and efficacy evaluated in vivo.

Methods : Quininib-hyaluronic acid (HA) microneedles were formulated via a salt precipitation method from a quininib-HA solution and cross-linked with 4-arm-PEG-amine prior to freeze-drying. Microneedle conformation was characterised by scanning electron microscopy. The zeta potential (charge) of the microneedles was determined by electrophoretic light scattering. Quininib released in vitro from the microneedles was quantified by HPLC. Anti-angiogenic activity was assessed in a zebrafish hyaloid developmental angiogenesis assay. The potential to ameliorate retinal vascular permeability after one month was determined using a cysteinyl leukotriene induced rodent model of retinal vascular permeability optimised by our lab and assessed by an Evan’s Blue assay.

Results : The quininib-HA formulation generated hollow needle-shaped particles with a charge of -35.5 mV. The majority of particles were >1.0 µm in size with 30% of particles ranging between 0.5-1.0 µm. The incorporation of quininib into these microneedles was 98%. In vitro, 20% quininib was released over 4 months; in the presence of increasing concentrations of hyaluronidase a maximum of 60% quininib was released over 4 months. Quininib released from these microparticles significantly inhibited hyaloid vessel development in zebrafish larvae (n=30) compared to control (p=<0.0001) and significantly inhibited retinal vascular permeability in Brown Norway rats (n=7) one month after administration compared to neat quininib control (p=0.0071).

Conclusions : Quininib-HA microneedles allow for sustained release of Quininib; are safe in vivo and quininib released from these microneedles effectively inhibits angiogenesis and retinal vascular permeability in vivo.

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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