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Development of a sustained release nano-in-gel delivery system for the chemotactic and angiogenic growth factor stromal-derived factor 1α

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posted on 08.02.2021, 11:09 by Joanne O'Dwyer, Megan Cullen, Sarinj Fattah, Robert Murphy, Smiljana Stefanovic, Lenka Kovarova, Martin Pravda, Vladimir Velebny, Andreas Heise, Garry Duffy, Sally-Ann Cryan
Stromal-Derived Factor 1α (SDF) is an angiogenic, chemotactic protein with significant potential for applications in a range of clinical areas, including wound healing, myocardial infarction and orthopaedic regenerative approaches. The 26-min in vivo half-life of SDF, however, has limited its clinical translation to date. In this study, we investigate the use of star-shaped or linear poly(glutamic acid) (PGA) polypeptides to produce PGA–SDF nanoparticles, which can be incorporated into a tyramine-modified hyaluronic acid hydrogel (HA–TA) to facilitate sustained localised delivery of SDF. The physicochemical properties and biocompatibility of the PGA–SDF nanoparticle formulations were extensively characterised prior to incorporation into a HA–TA hydrogel. The biological activity of the SDF released from the nano-in-gel system was determined on Matrigel®, scratch and Transwell® migration assays. Both star-shaped and linear PGA facilitated SDF nanoparticle formation with particle sizes from 255–305 nm and almost complete SDF complexation. Star-PGA–SDF demonstrated superior biocompatibility and was incorporated into a HA–TA gel, which facilitated sustained SDF release for up to 35 days in vitro. Released SDF significantly improved gap closure on a scratch assay, produced a 2.8-fold increase in HUVEC Transwell® migration and a 1.5-fold increase in total tubule length on a Matrigel® assay at 12 h compared to untreated cells. Overall, we present a novel platform system for the sustained delivery of bioactive SDF from a nano-in-gel system which could be adapted for a range of biomedical applications.

Funding

Science Foundation Ireland Investigator Award (IvP) grant number 13/IA/1840

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

Health Research Board Summer Studentship grant

Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM)

European Regional Development Fund (Grant 13/RC/2073).

History

Associated research data files

Supplementary material is available at: http://www.mdpi.com/1999-4923/12/6/513/s1

Comments

The original article is available at https://www.mdpi.com/

Published Citation

O'Dwyer J, Cullen M, Fattah S, Murphy R, Stefanovic S, Kovarova L, Pravda M, Velebny V, Heise A, Duffy GP, Cryan SA. Development of a sustained release nano-in-gel delivery system for the chemotactic and angiogenic growth factor stromal-derived factor 1α. Pharmaceutics.2020;12(6):513.

Publication Date

4 Jun 2020

PubMed ID

32512712

Department/Unit

  • School of Pharmacy and Biomolecular Sciences
  • RCSI Tissue Engineering Group (TERG)
  • Anatomy and Regenerative Medicine
  • Chemistry
  • Amber (Advanced Material & Bioengineering Research) Centre
  • Cu00daRAM Centre for Research in Medical Devices

Research Area

  • Respiratory Medicine
  • Chemistry and Pharmaceutical Sciences
  • Biomaterials and Regenerative Medicine

Publisher

MDPI AG

Version

  • Published Version (Version of Record)

Licence

Exports

Royal College of Surgeons in Ireland

Licence

Exports