Sustained VEGF delivery via PLGA nanoparticles promotes vascular growth
Open Access
- 1 June 2010
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Heart and Circulatory Physiology
- Vol. 298 (6), H1959-H1965
- https://doi.org/10.1152/ajpheart.00199.2009
Abstract
Technologies to increase tissue vascularity are critically important to the fields of tissue engineering and cardiovascular medicine. Currently, limited technologies exist to encourage angiogenesis and arteriogenesis in a controlled manner. In the present study, we describe an injectable controlled release system consisting of VEGF encapsulated in poly(lactic- co-glycolic acid) (PLGA) nanoparticles (NPs). The majority of VEGF was released gradually over 2–4 days from the NPs as determined by an ELISA release kinetics experiment. An in vitro aortic ring bioassay was used to verify the bioactivity of VEGF-NPs compared with empty NPs and no treatment. A mouse femoral artery ischemia model was then used to measure revascularization in VEGF-NP-treated limbs compared with limbs treated with naked VEGF and saline. 129/Sv mice were anesthetized with isoflurane, and a region of the common femoral artery and vein was ligated and excised. Mice were then injected with VEGF-NPs, naked VEGF, or saline. After 4 days, three-dimensional microcomputed tomography angiography was used to quantify vessel growth and morphology. Mice that received VEGF-NP treatment showed a significant increase in total vessel volume and vessel connectivity compared with 5 μg VEGF, 2.5 μg VEGF, and saline treatment (all P < 0.001). When the yield of the fabrication process was taken into account, VEGF-NPs were over an order of magnitude more potent than naked VEGF in increasing blood vessel volume. Differences between the VEGF-NP group and all other groups were even greater when only small-sized vessels under 300 μm diameter were analyzed. In conclusion, sustained VEGF delivery via PLGA NPs shows promise for encouraging blood vessel growth in tissue engineering and cardiovascular medicine applications.Keywords
This publication has 19 references indexed in Scilit:
- The effect of scaffold degradation rate on three-dimensional cell growth and angiogenesisBiomaterials, 2004
- Quantitative microcomputed tomography analysis of collateral vessel development after ischemic injuryAmerican Journal of Physiology-Heart and Circulatory Physiology, 2004
- The VIVA TrialCirculation, 2003
- Mouse aortic ring assay: A new approach of the molecular genetics of angiogenesisBiological Procedures Online, 2002
- Restoration of blood flow and evaluation of corresponding angiogenic events by scanning electron microscopy after a single dose of VEGF in a model of peripheral vascular diseaseAngiogenesis, 2002
- The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devicesBiomaterials, 2000
- Mouse model of angiogenesis.1998
- Influence of experimental parameters on the characteristics of poly(lactic acid) nanoparticles prepared by a double emulsion methodJournal of Controlled Release, 1998
- Intramuscular administration of vascular endothelial growth factor induces dose-dependent collateral artery augmentation in a rabbit model of chronic limb ischemia.1994
- Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model.JCI Insight, 1994