Pioglitazone-Incorporated Nanoparticles Prevent Plaque Destabilization and Rupture by Regulating Monocyte/Macrophage Differentiation in ApoE−/− Mice

Objective—Inflammatory monocytes/macrophages produce various proteinases, including matrix metalloproteinases, and degradation of the extracellular matrix by these activated proteinases weakens the mechanical strength of atherosclerotic plaques, which results in a rupture of the plaque. Peroxisome proliferator–activated receptor-γ induces a polarity shift of monocytes/macrophages toward less inflammatory phenotypes and has the potential to prevent atherosclerotic plaque ruptures. Therefore, we hypothesized that nanoparticle-mediated targeted delivery of the peroxisome proliferator–activated receptor-γ agonist pioglitazone into circulating monocytes could effectively inhibit plaque ruptures in a mouse model. Approach and Results—We prepared bioabsorbable poly(lactic-co-glycolic-acid) nanoparticles containing pioglitazone (pioglitazone-NPs). Intravenously administered poly(lactic-co-glycolic-acid) nanoparticles incorporated with fluorescein isothiocyanate were found in circulating monocytes and aortic macro...