Publication detail

Development of a Sustained Release Nano-In-Gel Delivery System for the Chemotactic and Angiogenic Growth Factor Stromal-Derived Factor 1 alpha

O'Dwyer,J.Cullen, MFattah, S.Murphy,R.Stefanovic, S. Kovarova, L. Pravda,M. Velebný, V. Heise, A.Duffy, G. Cryan, S.

Original Title

Development of a Sustained Release Nano-In-Gel Delivery System for the Chemotactic and Angiogenic Growth Factor Stromal-Derived Factor 1 alpha

Type

journal article in Web of Science

Language

English

Original Abstract

Stromal-Derived Factor 1 alpha (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(R), scratch and Transwell(R)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(R)migration and a 1.5-fold increase in total tubule length on a Matrigel(R)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.

Keywords

angiogenesis; stromal-derived factor; sustained release; nanoparticle; hydrogel; chemotaxis; protein delivery

Authors

O'Dwyer,J.;Cullen, M;Fattah, S.;Murphy,R.;Stefanovic, S.; Kovarova, L. ;Pravda,M. ;Velebný, V.; Heise, A.;Duffy, G.; Cryan, S.

Released

4. 6. 2020

Publisher

MDPI

Location

BASEL

ISBN

1999-4923

Periodical

Pharmaceutics

Year of study

12

Number

6

State

Swiss Confederation

Pages from

1

Pages to

25

Pages count

26

URL

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355599/

BibTex

@article{BUT165167,
  author="O'Dwyer,J. and Cullen, M and Fattah, S. and Murphy,R. and Stefanovic, S. and Kovarova, L. and Pravda,M. and Velebný, V. and Heise, A. and Duffy, G. and Cryan, S.",
  title="Development of a Sustained Release Nano-In-Gel Delivery System for the Chemotactic and Angiogenic Growth Factor Stromal-Derived Factor 1 alpha",
  journal="Pharmaceutics",
  year="2020",
  volume="12",
  number="6",
  pages="1--25",
  doi="10.3390/pharmaceutics12060513",
  issn="1999-4923",
  url="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355599/"
}