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Development of a Nanomedicine loaded Hydrogel for Sustained Delivery of an Angiogenic Growth Factor to the Ischaemic Myocardium

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posted on 19.03.2020 by Joanne O'Dwyer, Robert Murphy, Eimear B. Dolan, Lenka Kovarova, Vladimir Velebny, Andreas Heise, Garry P. Duffy, Sally-Ann Cryan
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.

Funding

Science Foundation Ireland 13/IA/1840

AMCARE consortium, a European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 604531.

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This article is also available at https://link.springer.com/article/10.1007/s13346-019-00684-5

Published Citation

O'Dwyer J, Murphy R, Dolan EB, Kavarova L, Pravda M, Velebny V, Heise A, Duffy GP, Cryan SA. Development of a nanomedicine-loaded hydrogel for sustained delivery of an angiogenic growth factor to the ischaemic myocardium.Drug Delivery and translational Research. 2020;10(2):440-454

Publication Date

05/11/2019

Publisher

Springer Nature

PubMed ID

31691161

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