Nanomedicine offers great potential for the treatment of cardiovascular disease and particulate systems have the capacity to markedly improve bioavailability of therapeutics. The delivery of pro-angiogenic hepatocyte growth factor (HGF) and pro-survival and pro-myogenic insulin-like growth factor (IGF-1) encapsulated in Alginate-Sulfate nanoparticles (AlgS-NP) might improve left ventricular (LV) functional recovery after myocardial infarction (MI). In a porcine ischemia-reperfusion model, MI is induced by 75 min balloon occlusion of the mid-left anterior descending coronary artery followed by reperfusion. After 1 week, pigs (n = 12) with marked LV-dysfunction (LV ejection fraction, LVEF < 45%) are randomized to fusion imaging-guided intramyocardial injections of 8 mg AlgS-NP prepared with 200 µg HGF and IGF-1 (HGF/IGF1-NP) or PBS (Control). Intramyocardial injection is safe and pharmacokinetic studies of Cy5-labeled NP confirm superior cardiac retention compared to intracoronary infusion. Seven weeks after intramyocardial-injection of HGF/IGF1-NP, infarct size, measured using magnetic resonance imaging, is significantly smaller than in controls and is associated with increased coronary flow reserve. Importantly, HGF/IGF1-NP-treated pigs show significantly increased LVEF accompanied by improved myocardial remodeling. These findings demonstrate the feasibility and efficacy of using AlgS-NP as a delivery system for growth factors and offer the prospect of innovative treatment for refractory ischemic cardiomyopathy.
Keywords: Hepatocyte growth factor; Insulin-like growth factor; Ischemia reperfusion injury; Ischemic cardiomyopathy; Nanoparticles.
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