Size-Dependent Ability of Liposomes to Accumulate in the Ischemic Myocardium and Protect the Heart

Abstract

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.

Evaluation of the In Vitro Cytotoxic Activity of Caffeic Acid Derivatives and Liposomal Formulation against Pancreatic Cancer Cell Lines

“…For this purpose, liposomes loaded with fluorescent Nile Red dye were used. Nanoparticle labeling with this hydrophobic dye, which fluoresces preferentially in non-polar environments, is commonly used for bioimaging studies [ 58 , 59 , 60 , 61 ]. Cellular uptake and localization were investigated by fluorescence microscopy.…”

Intravascular Imaging of Atherosclerosis by Using Engineered Nanoparticles

“…Due to their intrinsic hydrophilic and hydrophobic nature, liposomes have been extensively used to encapsulate a variety of therapeutic agents including proteins, nucleic acid, drugs, and diagnostic agents [ 37 ]. In cardiovascular research, earlier studies showed that liposomal particles can be accumulated in infarcted myocardium [ 38 ], and more recent studies suggest that liposome particles with sizes between 70 to 110 nm are associated with more capabilities to penetrate capillaries and be accumulated in the ischemic myocardium [ 39 ].…”

Three-dimensional, symmetrically assembled microfluidic device for lipid nanoparticle production

“…The size of LNPs plays an important role in both the LNP biodistribution and LNP performance, such as antitumor effect and gene silencing activity. [1][2][3][4][5][6][7] Generally, small-sized LNPs are desirable for stromal rich tumor tissues, such as pancreatic cancer. On the other hand, 100 nm-sized LNPs can deliver drugs or RNA into the hepatocytes of liver tissues passing through the fenestrae (with an approximate diameter of 100-150 nm).…”

“…However, LNPs are produced with a size distribution in spite of size tuning such as extrusion using a polycarbonate lter and ultra-sonication. 1,9 Therefore, a precise LNP size control method is indispensable for understanding the effect of the LNP size on the DDS performance.…”