3 years ago

VEGF Nanoparticles Repair Heart after Myocardial Infarction.

Suzanne Oparil, Anton V Borovjagin, Wuqiang Zhu, Yasin Oduk, Ramaswamy Kannappan, Jianyi Zhang, Meng Zhao
Vascular endothelial growth factor (VEGF) is a well characterized pro-angiogenic cytokine that has been shown to promote neovascularization in the hearts of patients with ischemic heart disease but can also lead to adverse effects, depending on the dose and mode of delivery. We investigated whether prolonged exposure to a low dose of VEGF could be achieved by encapsulating the VEGF in polylactic-co-glycolic acid (PLGA) nanoparticles and whether treatment with VEGF-containing nanoparticles improved cardiac function and protected against left ventricular (LV) remodeling in the hearts of mice with experimentally induced myocardial infarction (MI). PLGA nanoparticles with a mean diameter of ~113 nm were generated via double emulsion and loaded with VEGF; the encapsulation efficiency was 53.5±1.7% (107.1±3.3 ng VEGF per mg nanoparticles). In culture, the VEGF nanoparticles released VEGF continuously for at least 31 days, and in a murine MI model, VEGF nanoparticle administration was associated with significantly greater vascular density in the peri-infarct region, reductions in infarct size, and improvements in LV contractile function 4 weeks after treatment. Thus, our study provides proof-of-principle that nanoparticle-mediated delivery increases the angiogenic and therapeutic potency of VEGF for the treatment of ischemic heart disease.

Publisher URL: http://doi.org/10.1152/ajpheart.00471.2017

DOI: 10.1152/ajpheart.00471.2017

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