Abstract
: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 2 populations of liposomes (∼70 and 110 nm diameter) during ischemia and their effect on ischemia/reperfusion injury. Isolated rat hearts were subjected to 30 minutes of low-flow ischemia with the liposomes, followed by 30 minutes of liposome-free reperfusion. The liposomes were loaded with the fluorescent dye Nile Red to assess their accumulation in the myocardium. The cardiac functional recovery during reperfusion was evaluated using force–velocity characteristics and coronary flow (CF). Reperfusion injury was evaluated by lactate dehydrogenase release. In addition, CF and contractility were assessed in hearts perfused normally with 70 nm liposomes. There was a 6- and 4-fold greater accumulation of the small liposomes in the myocardium and mitochondria, respectively, compared with the large liposomes. Importantly, even without any incorporated drugs, both populations of liposomes improved functional recovery and reduced lactate dehydrogenase release. However, the smaller liposomes showed 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-stabilizing effect.
Highlights
There is significant scientific interest in the potential of liposomes to provide targeted delivery of drugs to damaged areas of the myocardium after myocardial infarction
The results of our experiments confirmed that the ability of the population of relatively small liposomes, produced by extrusion through 30 nm filters, to accumulate in the ischemic myocardium is significantly higher compared with the population of larger particles, prepared using 100 nm filters
Our results indicate that low-flow ischemia (LFI) of hearts with liposomes of either size provides successful transport of these particles into the ischemic myocardium
Summary
There is significant scientific interest in the potential of liposomes to provide targeted delivery of drugs to damaged areas of the myocardium after myocardial infarction. Any modification of the liposomes modulates their properties, their interaction with cells, and efficacy of drug delivery.[7,8] Importantly, pores can be formed in the capillaries located in the area of inflammation that can be caused by different pathological processes, including myocardial ischemia. These pores may become large enough allowing nanoparticles to penetrate the vascular barrier and accumulate in
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