Cardiovascular diseases are considered as one of the serious diseases that leads to the death of millions of people all over the world. Stent implantation has been approved as an easy and promising way to treat cardiovascular diseases. However, in-stent restenosis and thrombosis remain serious problems after stent implantation. It was demonstrated in a large body of previously published literature that endothelium impairment represents a major factor for restenosis. This discovery became the driving force for many studies trying to achieve an optimized methodology for accelerated re-endothelialization to prevent restenosis. Thus, in this review, we summarize the different methodologies opted to achieve re-endothelialization, such as, but not limited to, manipulation of surface chemistry and surface topography.

The sustained or controlled release of nitric oxide (NO) can be the most promising approach for the suppression or prevention of restenosis and thrombosis caused by stent implantation. The aim of this study is to investigate the feasibility in the potential use of layer-by-layer (LBL) coating with a NO donor-containing liposomes to control the release rate of NO from a metallic stent. Microscopic observation and surface characterizations of LBL-modified stents demonstrate successful LBL coating with liposomes on a stent. Release profiles of NO show that the release rate is sustained up to 5 d. In vitro cell study demonstrates that NO release significantly enhances endothelial cell proliferation, whereas it markedly inhibits smooth muscle cell proliferation. Finally, in vivo study conducted with a porcine coronary injury model proves the therapeutic efficacy of the NO-releasing stents coated by liposomal LBL technique, supported by improved results in luminal healing, inflammation, and neointimal thickening except thrombo-resistant effect. As a result, all these results demonstrate that highly optimized release rate and therapeutic dose of NO can be achieved by LBL coating and liposomal encapsulation, followed by significantly efficacious outcome in vivo.

Nitric oxide (NO) is crucial for body homeostasis at moderate levels, but cytotoxic at high levels, thus making it a potential candidate for anticancer therapies and antibacterial surface coatings. To date, NO use has been limited due to its very short half-life. Many strategies have been utilized in an attempt to control the half-life of NO, including (but not limited to) lipid-based carriers, due to their biocompatibility and versatility. Areas covered: In this review, we discuss the latest studies that aimed to control the release of NO via a variety of lipid-based delivery carriers, such as liposomes (echogenic and normal) and microbubbles. In addition, we discuss the different types of NO donors used to control and target the release of NO. Expert opinion: Achieving a NO releasing lipid-based systems to mimic the natural release rate of NO remains a challenging task. Many promising strategies are still to be tackled, such as NO release supported lipid bilayers using GPx mimicking catalysts instead of vesicles, or the use of lipophillic NO donors such as nitrooleate instead of the conventional hydrophilic NO donors. These new strategies may present us with better alternatives to the previously published systems.