Passive targeting of lipid-based nanoparticles to mouse cardiac ischemia-reperfusion injury.

Reperfusion therapy is commonly applied after a myocardial infarction. Reperfusion, however, causes secondary damage. An emerging approach for treatment of ischemia-reperfusion (IR) injury involves the delivery of therapeutic nanoparticles to the myocardium to promote cell survival and constructively influence scar formation and myocardial remodeling. The aim of this study was to provide detailed understanding of the in vivo accumulation and distribution kinetics of lipid-based nanoparticles (micelles and liposomes) in a mouse model of acute and chronic IR injury. Both micelles and liposomes contained paramagnetic and fluorescent lipids and could therefore be visualized with magnetic resonance imaging (MRI) and confocal laser scanning microscopy (CLSM). In acute IR injury both types of nanoparticles accumulated massively and specifically in the infarcted myocardium as revealed by MRI and CLSM. Micelles displayed faster accumulation kinetics, probably owing to their smaller size. Liposomes occasionally co-localized with vessels and inflammatory cells. In chronic IR injury only minor accumulation of micelles was observed with MRI. Nevertheless, CLSM revealed specific accumulation of both micelles and liposomes in the infarct area 3 h after administration. Owing to their specific accumulation in the infarcted myocardium, lipid-based micelles and liposomes are promising vehicles for (visualization of) drug delivery in myocardial infarction.