Distribution of Systemically Administered Nanoparticles Reveals a Size-Dependent Effect Immediately following Cardiac Ischaemia-Reperfusion Injury.

David J Lundy,Elsie K-W Toh,Kun-Hung Chen,Patrick C-H Hsieh

doi:10.1038/srep25613

Abstract

Nanoparticles represent an attractive option for systemic delivery of therapeutic compounds to the heart following myocardial infarction. However, it is well known that physicochemical properties of nanoparticles such as size, shape and surface modifications can vastly alter the distribution and uptake of injected nanoparticles. Therefore, we aimed to provide an examination of the rapid size-dependent uptake of fluorescent PEG-modified polystyrene nanoparticles administered immediately following cardiac ischaemia-reperfusion injury in mice. By assessing the biodistribution of nanoparticles with core diameters between 20 nm and 2 μm 30 minutes after their administration, we conclude that 20–200 nm diameter nanoparticles are optimal for passive targeting of the injured left ventricle.

Highlights

Researchers have explored a broad range of therapeutic approaches, aiming to reduce cardiomyocyte death, lessen the degree of ventricular remodelling, and improve cardiac function following cardiac ischaemia
We have found that a wide size range of nanoparticles will co-localise with the heart soon after I/R injury
We conclude that nanoparticles with a core diameter in the 20–200 nm range are optimal for rapid passive targeting of the I/R-injured left ventricle

Summary

Introduction

Researchers have explored a broad range of therapeutic approaches, aiming to reduce cardiomyocyte death, lessen the degree of ventricular remodelling, and improve cardiac function following cardiac ischaemia. Direct myocardial injection is highly invasive, volume-limited and has the potential to cause further injury to the already-weakened myocardium Another option for delivery to the myocardium is intracoronary catheterisation, where therapeutics are delivered directly into the coronary artery. There is some previous evidence to show that the damage induced by ischaemia-reperfusion injury alters vascular permeability in the heart[24,25] This “leaky” vasculature alone is not sufficient to ensure optimal delivery of therapeutic compounds[26]. With reference to the heart, a previous study has shown that nano-carrier size (15 nm micelle vs 100 nm liposome) alters retention in the infarcted region following permanent coronary artery occlusion[36]. A previous study in our lab has demonstrated a size-dependent effect on nanoparticle retention by the infarcted heart, even after direct myocardial injection[20]

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