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

Pharmaceutics

Robert Murphy¹  Joanne O’Dwyer²  Megan Cullen²  Smiljana Stefanovic²  SallyAnn Cryan²  Sarinj Fattah²  Lenka Kovarova³  Martin Pravda³  Vladimir Velebny³  Andreas Heise⁴  GarryP. Duffy⁵ 

[1] Department of Chemistry, Royal College of Surgeons in Ireland (RCSI), Dublin 2, Ireland;Drug Delivery & Advanced Materials Team, School of Pharmacy & Biomolecular Sciences, Royal College of Surgeons in Ireland (RCSI), Dublin 2, Ireland;R & D Department, Contipro, Dolni Dobrouc 401, 561 02 Dolni Dobrouc, Czech Republic;SFI Research Centre for Medical Devices (CURAM), National University of Ireland Galway (NUIG) & Royal College of Surgeons in Ireland (RCSI), Galway and Dublin, Ireland;Trinity Centre for Biomedical Engineering, Trinity College Dublin (TCD), Dublin 2, Ireland;

关键词: angiogenesis;    stromal-derived factor;    sustained release;    nanoparticle;    hydrogel;    chemotaxis;   

DOI  :  10.3390/pharmaceutics12060513

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown