Sustained delivery of vascular endothelial growth factor using a dextran/poly(lactic-co-glycolic acid)-combined microsphere system for therapeutic neovascularization
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We hypothesize that the controlled delivery of vascular endothelial growth factor (VEGF) using a novel protein sustained-release system based on the combination of protein-loaded dextran microparticles and PLGA microspheres could be useful to achieve mature vessel formation in a rat hind-limb ischemic model. VEGF-loaded dextran microparticles were fabricated and then encapsulated into poly(lactic-co-glycolic acid) (PLGA) microspheres to prepare VEGF–dextran–PLGA microspheres. The release behavior and bioactivity in promoting endothelial cell proliferation of VEGF from PLGA microspheres were monitored in vitro. VEGF–dextran–PLGA microsphere-loaded fibrin gel was injected into an ischemic rat model, and neovascularization at the ischemic site was evaluated. The release of VEGF from PLGA microspheres was in a sustained manner for more than 1 month in vitro with low level of initial burst release. The released VEGF enhanced the proliferation of endothelial cells in vitro, and significantly promoted the capillaries and smooth muscle α-actin positive vessels formation in vivo. The retained bioactivity of VEGF released from VEGF–dextran–PLGA microspheres potentiated the angiogenic efficacy of VEGF. This sustained-release system may be a promising vehicle for delivery of multiple angiogenic factors for therapeutic neovascularization.
KeywordsVascular endothelial growth factor Microsphere Sustained release Ischemia Neovascularization
This study was funded by National Natural Science Foundation of China (grant number 81460083), Natural Science Foundation of Jiangxi Province (grant number 20141BBG70032, 20152ACB21026 and 20142BAB215034).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.
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