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O’DWYER, J. MURPHY, R. GONZÁLEZ-VÁZQUEZ, A. KOVÁŘOVÁ, L. PRAVDA, M. VELEBNÝ, V. HEISE, A. DUFFY, G. CRYAN, S.
Original Title
Translational Studies on the Potential of a VEGF Nanoparticle-Loaded Hyaluronic Acid Hydrogel
Type
journal article in Web of Science
Language
English
Original Abstract
Heart 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.
Keywords
vascular endothelial growth factor nanoparticles; hyaluronic acid hydrogel; nanoparticle-loaded hydrogel; angiogenic growth factor; sustained release; catheter delivery; chick chorioallantoic membrane model; protein delivery
Authors
O’DWYER, J.; MURPHY, R.; GONZÁLEZ-VÁZQUEZ, A.; KOVÁŘOVÁ, L.; PRAVDA, M.; VELEBNÝ, V.; HEISE, A.; DUFFY, G.; CRYAN, S.
Released
22. 5. 2021
Publisher
MDPI
Location
BASEL
ISBN
1999-4923
Periodical
Pharmaceutics
Year of study
13
Number
6
State
Swiss Confederation
Pages from
1
Pages to
19
Pages count
URL
https://doi.org/10.3390/pharmaceutics13060779
Full text in the Digital Library
http://hdl.handle.net/11012/204969
BibTex
@article{BUT177316, author="Joanne {O’Dwyer} and Robert {Murphy} and Arlyng {González-Vázquez} and Lenka {Kovářová} and Martin {Pravda} and Vladimír {Velebný} and Andreas {Heise} and Garry P. {Duffy} and Sally Ann {Cryan}", title="Translational Studies on the Potential of a VEGF Nanoparticle-Loaded Hyaluronic Acid Hydrogel", journal="Pharmaceutics", year="2021", volume="13", number="6", pages="1--19", doi="10.3390/pharmaceutics13060779", issn="1999-4923", url="https://doi.org/10.3390/pharmaceutics13060779" }