Atherosclerosis is the leading cause of death in developed countries. The pathogenetic mechanism relies on a macrophage-based immune reaction to low density lipoprotein (LDL) deposition in blood vessels with dysfunctional endothelia. Thus, atherosclerosis is defined as a chronic inflammatory disease. A plethora of cardiovascular drugs have been developed and are on the market, but the major shortcoming of standard medications is that they do not address the root cause of the disease. Statins and thiazolidinediones that have recently been recognized to exert specific anti-atherosclerotic effects represent a potential breakthrough on the horizon. But their whole potential cannot be realized due to insufficient availability at the pathological site and severe off-target effects. The focus of this review will be to elaborate how both groups of drugs could immensely profit from nanoparticulate carriers. This delivery principle would allow for their accumulation in target macrophages and endothelial cells of the atherosclerotic plaque, increasing bioavailability where it is needed most. Based on the analyzed literature we conclude design criteria for the delivery of statins and thiazolidinediones with nanoparticles for anti-atherosclerotic therapy. Nanoparticles need to be below a diameter of 100 nm to accumulate in the atherosclerotic plaque and should be fabricated using biodegradable materials. Further, the thiazolidinediones or statins must be encapsulated into the particle core, because especially for thiazolidindiones the uptake into cells is prerequisite for their mechanism of action. For optimal uptake into targeted macrophages and endothelial cells, the ideal particle should present ligands on its surface which bind specifically to scavenger receptors. The impact of statins on the lectin-type oxidized LDL receptor 1 (LOX1) seems particularly promising because of its outstanding role in the inflammatory process. Using this pioneering concept, it will be possible to promote the impact of statins and thiazolidinediones on macrophages and endothelial cells and significantly enhance their anti-atherosclerotic therapeutic potential.
Copyright © 2021. Published by Elsevier B.V.