Size-dependent ability of liposomes to accumulate in the ischaemic myocardium and protect the heart

Liposomes have the potential to be used for drug delivery. Meanwhile, liposome size may affect their accumulation in the target tissue. We investigated the myocardial accumulation of two populations of liposomes (~70 and 110 nm diameter) during ischaemia and their effect on ischaemia/reperfusion injury.
Isolated rat hearts were subjected to 30 min low-flow ischemia with the liposomes followed by 30 min liposome-free reperfusion. The liposomes were loaded with the fluorescent dye Nile Red to assess their accumulation in myocardium. The cardiac functional recovery during reperfusion was evaluated using force-velocity characteristics and coronary flow (CF). Reperfusion injury was evaluated by lactate dehydrogenase (LDH) release. Additionally, CF and contractility were assessed in hearts perfused normally with 70 nm liposomes.
There was a six- and four-fold greater accumulation of the small liposomes in myocardium and mitochondria, respectively, compared to the large liposomes. Importantly, even without any incorporated drugs, both populations of liposomes improved functional recovery and reduced LDH release. However, the smaller liposomes showed a significantly higher protective and vasodilatory effects during reperfusion than the larger particles. These liposomes also increased CF and contractility during normal perfusion. We suggest that the protective properties of the liposomes could be related to their membrane-stabilising effect.