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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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Drug Delivery & Advanced Materials Team, School of Pharmacy & Biomolecular Sciences, Royal College of Surgeons in Ireland (RCSI), Dublin 2, Ireland
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Tissue Engineering Research Group, Department of Anatomy & Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), Dublin 2, Ireland
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Trinity Centre for Biomedical Engineering, Trinity College Dublin (TCD), Dublin 2, Ireland
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SFI Research Centre for Medical Devices (CURAM), National University of Ireland Galway (NUIG) & Royal College of Surgeons in Ireland (RCSI), Galway and Dublin, Ireland
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Department of Chemistry, Royal College of Surgeons in Ireland (RCSI), Dublin 2, Ireland
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R & D Department, Contipro, Dolni Dobrouc 401, 561 02 Dolni Dobrouc, Czech Republic
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Faculty of Chemistry, Institute of Physical Chemistry, Brno University of Technology, Purkynova 464/118, 612 00 Brno, Czech Republic
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The SFI Centre for Advanced Materials and Bioengineering Research (AMBER), National University of Ireland Galway (NUIG), Royal College of Surgeons in Ireland (RCSI) & Trinity College Dublin (TCD), Dublin, Ireland
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Anatomy, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway (NUIG), Galway, Ireland
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(6), 513; https://doi.org/10.3390/pharmaceutics12060513
Received: 3 April 2020 / Revised: 14 May 2020 / Accepted: 28 May 2020 / Published: 4 June 2020
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. View Full-Text
Keywords: angiogenesis; stromal-derived factor; sustained release; nanoparticle; hydrogel; chemotaxis; protein delivery angiogenesis; stromal-derived factor; sustained release; nanoparticle; hydrogel; chemotaxis; protein delivery
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MDPI and ACS Style

O’Dwyer, J.; Cullen, M.; Fattah, S.; Murphy, R.; Stefanovic, S.; Kovarova, L.; Pravda, M.; Velebny, V.; Heise, A.; Duffy, G.P.; Cryan, S.A. Development of a Sustained Release Nano-In-Gel Delivery System for the Chemotactic and Angiogenic Growth Factor Stromal-Derived Factor 1α. Pharmaceutics 2020, 12, 513.

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