Distribution of lipid-based nanoparticles to infarcted myocardium with potential application for MRI-monitored drug delivery

Abstract

Adverse cardiac remodeling after myocardial infarction ultimately causes heart failure. To stimulate reparative processes in the infarct, efficient delivery and retention of therapeutic agents is desired. This might be achieved by encapsulation of drugs in nanoparticles.The goal of this study was to characterize the distribution pattern of differently sized long-circulating lipid-based nanoparticles, namely micelles (~15nm) and liposomes (~100nm), in a mouse model of myocardial infarction (MI). MI was induced in mice (n=38) by permanent occlusion of the left coronary artery. Nanoparticle accumulation following intravenous administration was examined one day and one week after surgery, representing the acute and chronic phase of MI, respectively. In vivo magnetic resonance imaging of paramagnetic lipids in the micelles and liposomes was employed to monitor the trafficking of nanoparticles to the infarcted myocardium. Ex vivo high-resolution fluorescence microscopy of fluorescent lipids was used to determine the exact location of the nanoparticles in the myocardium.In both acute and chronic MI, micelles permeated the entire infarct area, which renders them very suited for the local delivery of cardioprotective or anti-remodeling drugs. Liposomes displayed slower and more restricted extravasation from the vasculature and are therefore an attractive vehicle for the delivery of pro-angiogenic drugs. Importantly, the ability to non-invasively visualize both micelles and liposomes with MRI creates a versatile approach for the development of effective cardioprotective therapeutic interventions.