Translational Studies on the Potential of a VEGF Nanoparticle-Loaded Hyaluronic Acid Hydrogel

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dc.contributor.authorO’Dwyer, Joannecs
dc.contributor.authorMurphy, Robertcs
dc.contributor.authorGonzález-Vázquez, Arlyngcs
dc.contributor.authorKovářová, Lenkacs
dc.contributor.authorPravda, Martincs
dc.contributor.authorVelebný, Vladimírcs
dc.contributor.authorHeise, Andreascs
dc.contributor.authorDuffy, Garry P.cs
dc.contributor.authorCryan, Sally Anncs
dc.coverage.issue6cs
dc.coverage.volume13cs
dc.date.accessioned2022-06-09T14:52:01Z
dc.date.available2022-06-09T14:52:01Z
dc.date.issued2021-05-22cs
dc.description.abstractHeart failure has a five-year mortality rate approaching 50%. Inducing angiogenesis following a myocardial infarction is hypothesized to reduce cardiomyocyte death and tissue damage, thereby preventing heart failure. Herein, a novel nano-in-gel delivery system for vascular endothelial growth factor (VEGF), composed of star-shaped polyglutamic acid-VEGF nanoparticles in a tyramine-modified hyaluronic acid hydrogel (nano-VEGF-HA-TA), is investigated. The ability of the nano-VEGF-HA-TA system to induce angiogenesis is assessed in vivo using a chick chorioallantoic membrane model (CAM). The formulation is then integrated with a custom-made, clinically relevant catheter suitable for minimally invasive endocardial delivery and the effect of injection on hydrogel properties is examined. Nano-VEGF-HA-TA is biocompatible on a CAM assay and significantly improves blood vessel branching (p < 0.05) and number (p < 0.05) compared to a HA-TA hydrogel without VEGF. Nano-VEGF-HA-TA is successfully injected through a 1.2 m catheter, without blocking or breaking the catheter and releases VEGF for 42 days following injection in vitro. The released VEGF retains its bioactivity, significantly improving total tubule length on a Matrigel(R) assay and human umbilical vein endothelial cell migration on a Transwell(R) migration assay. This VEGF-nano in a HA-TA hydrogel delivery system is successfully integrated with an appropriate device for clinical use, demonstrates promising angiogenic properties in vivo and is suitable for further clinical translation.en
dc.formattextcs
dc.format.extent1-19cs
dc.format.mimetypeapplication/pdfcs
dc.identifier.citationPharmaceutics. 2021, vol. 13, issue 6, p. 1-19.en
dc.identifier.doi10.3390/pharmaceutics13060779cs
dc.identifier.issn1999-4923cs
dc.identifier.other177316cs
dc.identifier.urihttp://hdl.handle.net/11012/204969
dc.language.isoencs
dc.publisherMDPIcs
dc.relation.ispartofPharmaceuticscs
dc.relation.urihttps://doi.org/10.3390/pharmaceutics13060779cs
dc.rightsCreative Commons Attribution 4.0 Internationalcs
dc.rights.accessopenAccesscs
dc.rights.sherpahttp://www.sherpa.ac.uk/romeo/issn/1999-4923/cs
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/cs
dc.subjectvascular endothelial growth factor nanoparticlesen
dc.subjecthyaluronic acid hydrogelen
dc.subjectnanoparticle-loaded hydrogelen
dc.subjectangiogenic growth factoren
dc.subjectsustained releaseen
dc.subjectcatheter deliveryen
dc.subjectchick chorioallantoic membrane modelen
dc.subjectprotein deliveryen
dc.titleTranslational Studies on the Potential of a VEGF Nanoparticle-Loaded Hyaluronic Acid Hydrogelen
dc.type.driverarticleen
dc.type.statusPeer-revieweden
dc.type.versionpublishedVersionen
sync.item.dbidVAV-177316en
sync.item.dbtypeVAVen
sync.item.insts2022.06.09 16:52:01en
sync.item.modts2022.06.09 16:14:24en
thesis.grantorVysoké učení technické v Brně. Fakulta chemická. Fakulta chemickács
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