Qutachi, O. orcid.org/0000-0002-5026-7358, Bullock, A.J. orcid.org/0000-0003-0579-3997, Gigliobianco, G. et al. (1 more author) (2019) Spatiotemporal release of VEGF from biodegradable polylactic-co-glycolic acid microspheres induces angiogenesis in chick chorionic allantoic membrane assay. International Journal of Pharmaceutics, 561. pp. 236-243. ISSN 0378-5173
Abstract
While vascular endothelial growth factor (VEGF) is an acknowledged potent pro-angiogenic agent there is a need to deliver it at an appropriate concentration for several days to achieve angiogenesis. The aim of this study was to produce microspheres of biodegradable polylactic-co-glycolic acid (PLGA) tailored to achieve sustained release of VEGF at an appropriate concentration over seven days, avoiding excessive unregulated release of VEGF that has been associated with the formation of leaky blood vessels. Several formulations were examined to produce microspheres loaded with both human serum albumin (HSA) and VEGF to achieve release of VEGF between 3 and 10 ng per ml for seven days to match the therapeutic window desired for angiogenesis. In vitro experiments showed an increase in endothelial cell proliferation in response to microspheres bearing VEGF. Similarly, when microspheres containing VEGF were added to the chorionic membrane of fertilised chicken eggs, there was an increase in the development of blood vessels over seven days in response, which was significant for microspheres bearing VEGF and HSA, but not VEGF alone. There was an increase in both blood vessel density and branching – both signs of proangiogenic activity. Further, there was clearly migration of cells to the VEGF loaded microspheres. In summary, we describe the development of an injectable delivery vehicle to achieve spatiotemporal release of physiologically relevant levels of VEGF for several days and demonstrate the angiogenic response to this. We propose that such a treatment vehicle would be suitable for the treatment of ischemic tissue or wounds.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | Crown Copyright © 2019 |
Keywords: | Angiogenesis; Chorioallantoic membrane; Polylactic-co-glycolic acid; Sustained release; Vascular endothelial growth factor; Animals; Biodegradable Plastics; Cell Proliferation; Chickens; Chorion; Delayed-Action Preparations; Drug Compounding; Drug Liberation; Endothelial Cells; Humans; Microspheres; Neovascularization, Physiologic; Polylactic Acid-Polyglycolic Acid Copolymer; Serum Albumin; Vascular Endothelial Growth Factor A |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Engineering (Sheffield) > School of Chemical, Materials and Biological Engineering The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Materials Science and Engineering (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 13 Dec 2024 09:43 |
Last Modified: | 13 Dec 2024 09:43 |
Status: | Published |
Publisher: | Elsevier BV |
Refereed: | Yes |
Identification Number: | 10.1016/j.ijpharm.2019.03.015 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:220781 |