Atorvastatin-based nanoparticle-decorated glyceryl monostearate as a targeted drug carrier for inhibition of atherosclerosis lesions

Abstract

Macrophages play a significant role in various phases of a chronic atherosclerotic plaque of the arterial wall. Oxidized low-density lipoprotein (Ox-LDL) accumulation in the tunica intima of an artery causes endothelial dysfunction in atherosclerosis. Statins are utilized to treat atherosclerosis, but they carry numerous adverse effects and inadequate therapeutic effects. Herein, atorvastatin nanoparticles (ATR NPs) are designed for treating atherosclerosis and enhancing the prolonged therapeutic efficacy related to the treatment of atherosclerotic plaques. For the synthesis of the ATR NPs, we have used atorvastatin-decorated glyceryl monostearate (GMS) in conjunction with ultra-sonication techniques. The GMS loaded ATR NPs were verified with characterization using multiple techniques to study their physicochemical properties. The synthesized ATR NPs revealed excellent stability, greater drug encapsulation efficiency (76.84 ± 4.7), and a sustained drug release profile, making them suitable for drug delivery systems. Live/dead staining and flow cytometry analysis showed that ATR NPs prevented cellular apoptosis and improved foam cell survival. Confocal microscopy images of ATR NPs associated with rhodamine 6G (Rh-6G) drugs revealed that ATR NPs improved cell uptake and internalization through endocytosis pathways. Using Oil Red O (ORO) staining, ATR NPs increased cholesterol efflux from arterial walls and clearance of apoptotic cells. ATR NPs reduced plaque buildup in atherosclerotic apoE^−/− mice after intravenous administration. These findings illustrate that ATR nanoparticles are more effective for treatment of atherosclerotic lesions.