Abstract 15381: Nanoparticle-mediated Delivery of Pioglitazone Ameliorates Inflammation and Inhibits Atherosclerotic Plaque Rupture in Apolipoprotein-E Deficient Mice

Background: Monocytes/macrophages play major roles in atherosclerotic plaque destabilization and rupture. Although PPARγ agonist including pioglitazone enhances alternative activation of monocytes/macrophages, its clinical use is hampered by adverse effects including heart failure. Therefore, we hypothesized that nanoparticle (NP)-mediated delivery of pioglitazone regulates monocytes/macrophages polarity and inhibits plaque rupture. Methods and Results: We developed bioabsorbable poly-lactic-glycolic-acid (PLGA) NP for effective drug delivery to atherosclerotic plaques. FACS analysis 2 days after intravenous injection of FITC-NP revealed that the NPs were effectively delivered to both circulating monocytes and aortic macrophages. Single injection of pioglitazone-NP (pio-NP) reduced circulating Ly6Chigh monocytes. Weekly intravenous administration of pio-NP (containing 0.7 or 7 mg/kg pioglitazone) for 4 weeks reduced atherosclerotic plaque rupture in the brachiocephalic arteries of apolipoprotein E-deficie...