pharmaceutics-12-00513-v2 (1).pdf (4.1 MB)
Development of a sustained release nano-in-gel delivery system for the chemotactic and angiogenic growth factor stromal-derived factor 1α
journal contributionposted on 2021-02-08, 11:09 authored by Joanne O'Dwyer, Megan Cullen, Sarinj FattahSarinj Fattah, Robert MurphyRobert Murphy, Smiljana Stefanovic, Lenka Kovarova, Martin Pravda, Vladimir Velebny, Andreas HeiseAndreas Heise, Garry DuffyGarry Duffy, Sally-Ann CryanSally-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.
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).
Data Availability StatementSupplementary material is available at: http://www.mdpi.com/1999-4923/12/6/513/s1
CommentsThe original article is available at https://www.mdpi.com/
Published CitationO'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 Date4 Jun 2020
- School of Pharmacy and Biomolecular Sciences
- RCSI Tissue Engineering Group (TERG)
- Anatomy and Regenerative Medicine
- Amber (Advanced Material & Bioengineering Research) Centre
- Cu00daRAM Centre for Research in Medical Devices
- Respiratory Medicine
- Chemistry and Pharmaceutical Sciences
- Biomaterials and Regenerative Medicine
- Published Version (Version of Record)