Abstract 4124070: Dual-action Nanomatrix Coated Stent for Improving Endothelialization while Suppressing Restenosis and Inflammation

Abstract

Introduction: The most common cause of cardiovascular disease (CVD) is atherosclerosis. The progression of atherosclerosis is characterized by endothelial cell dysfunction, proliferation of smooth muscle cell proliferation, and plaques which lead to progressive arterial stenosis. Bare metal stents (BMS) were developed to hinder stenosis, but re-stenosis has been observed following deployment. Drug-eluting stents (DES) have been developed to mitigate this, by releasing anti-proliferative drugs to suppress smooth muscle cell proliferation. However, these drugs also suppress endothelial growth. To address this, we are developing and evaluating a dual action nanomatrix coated stent comprised of a nitric oxide (NO) releasing peptide amphiphile (PA) and everolimus-encapsulated liposomes to improve endothelial proliferation and suppressing smooth muscle cell proliferation and inflammation. Materials and Methods: The nanomatrix coating contains a PA generated via solid phase peptide synthesis consisting of a nitric oxide donor and a cell adhesive ligand. The everolimus-encapsulated liposomes were prepared with DPPC, DOTAP, DSPE-PEG, and cholesterol via thin film rehydration, followed by encapsulation with everolimus. TEM was performed on liposomes to assess their stability. The release kinetics were evaluated via UV-vis of samples containing released everolimus. To evaluate the dual effect of the nanomatrix coating on metabolism, NO and everolimus were used to treat endothelial and smooth muscle cells, and an MTT assay was done. Results and Discussion: TEM showed that liposomes maintained stability over time. It was found that 60% of everolimus was released by day 30. The MTT assay showed that NO with everolimus increased endothelial cell metabolic activity and maintained or lowered smooth muscle cell activity compared to everolimus alone. Conclusions: Everolimus-encapsulated liposomes have potential as an effective delivery method of everolimus. NO and everolimus have a synergistic effect of improving endothelial function and suppressing smooth muscle cells.