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Development of a nanomedicine-loaded hydrogel for sustained delivery of an angiogenic growth factor to the ischaemic myocardium

  • Joanne O’Dwyer
  • Robert Murphy
  • Eimear B. Dolan
  • Lenka Kovarova
  • Martin Pravda
  • Vladimir Velebny
  • Andreas Heise
  • Garry P. Duffy
  • Sally Ann CryanEmail author
Original Article

Abstract

The 5-year mortality rate for heart failure borders on 50%. The main cause is an ischaemic cardiac event where blood supply to the tissue is lost and cell death occurs. Over time, this damage spreads and the heart is no longer able to pump efficiently. Increasing vascularisation of the affected area has been shown to reduce patient symptoms. The growth factors required to do this have short half-lives making development of an efficacious therapy difficult. Herein, the angiogenic growth factor Vascular Endothelial Growth Factor (VEGF) is complexed electrostatically with star-shaped or linear polyglutamic acid (PGA) polypeptides. Optimised PGA-VEGF nanomedicines provide VEGF encapsulation of > 99% and facilitate sustained release of VEGF for up to 28 days in vitro. The star-PGA-VEGF nanomedicines are loaded into a percutaneous delivery compliant hyaluronic acid hydrogel. Sustained release of VEGF from the composite nano-in-gel system is evident for up to 35 days and the released VEGF has comparable bioactivity to free, fresh VEGF when tested on both Matrigel® and scratch assays. The final star-PGA-VEGF nanomedicine-loaded hydrogel is biocompatible and provides sustained release of bioactive VEGF. Therefore, we report the development of novel, self-assembling PGA-VEGF nanomedicines and their incorporation into a hyaluronic acid hydrogel that is compatible with medical devices to enable minimally invasive delivery to the heart. The final star-PGA-VEGF nanomedicine-loaded hydrogel is biocompatible and provides sustained release of bioactive VEGF. This formulation provides the basis for optimal spatiotemporal delivery of an angiogenic growth factor to the ischaemic myocardium.

Keywords

Star polypeptide Nanoparticle Angiogenesis Growth factor Ischaemia 

Notes

Acknowledgements

The authors acknowledge the support of Brenton Cavanagh for assistance with imaging and Matrigel® analysis.

Funding information

Financial support for this project was provided by Science Foundation Ireland (SFI) under an Investigator Award grant number 13/IA/1840 and the AMCARE consortium, a European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 604531.

Supplementary material

13346_2019_684_MOESM1_ESM.pdf (443 kb)
ESM 1 (PDF 553 kb)

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Copyright information

© Controlled Release Society 2019

Authors and Affiliations

  • Joanne O’Dwyer
    • 1
    • 2
    • 3
  • Robert Murphy
    • 4
  • Eimear B. Dolan
    • 1
    • 2
  • Lenka Kovarova
    • 5
    • 6
  • Martin Pravda
    • 5
  • Vladimir Velebny
    • 5
  • Andreas Heise
    • 4
    • 7
    • 8
  • Garry P. Duffy
    • 2
    • 3
    • 7
    • 8
    • 9
  • Sally Ann Cryan
    • 1
    • 2
    • 3
    • 7
    • 8
    Email author
  1. 1.Drug Delivery & Advanced Materials TeamSchool of Pharmacy & Biomolecular Sciences, Royal College of Surgeons in Ireland (RCSI)Dublin 2Ireland
  2. 2.Tissue Engineering Research Group, Department of Anatomy & Regenerative MedicineRCSIDublin 2Ireland
  3. 3.Trinity Centre for Biomedical EngineeringTrinity College Dublin (TCD)Dublin 2Ireland
  4. 4.Department of ChemistryRCSIDublin 2Ireland
  5. 5.R&D DepartmentContiproDolni DobroucCzech Republic
  6. 6.Faculty of Chemistry, Institute of Physical ChemistryBrno University of TechnologyBrnoCzech Republic
  7. 7.CÚRAM, SFI Research Centre for Medical DevicesNational University of Ireland Galway (NUIG) & RCSIGalwayIreland
  8. 8.AMBER, the SFI Centre for Advanced Materials and BioengineeringNUIG, RCSI & TCDDublinIreland
  9. 9.Anatomy, School of Medicine, College of Medicine, Nursing and Health SciencesNUIGGalwayIreland

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