Nitric oxide from nanoparticles and applications to cardiovascular health

The current limitations of nitric oxide (NO) delivery systems has stimulated an extraordinary interest in the development of platforms that generate and release NO in a controlled and sustained manner, with a heavy emphasis on the treatment of cardiovascular disease states. This chapter describes the positive achievements of NO-releasing nanoparticles (NO-np) prepared using a novel platform based on hydrogel/glass hybrid nanoparticles capable of storing significant amounts of NO generated through thermal reduction of nitrite. The simplicity of the control release rate of NO from NO-np is regulated by its hydration when exposed to moisture; therefore, it allows the nanoparticles to slowly release therapeutic levels of NO. In a dose-dependent manner, infusion of NO-np has significant direct cardiovascular effect on physiological conditions, in terms of decreasing blood pressure, increasing exhaled NO, inducing vasodilation and increasing microvascular perfusion, during several hours post-infusion. Furthermore, the NO released by the NO-np prevents the inflammatory response regenerated by immune response to macroscopic external agents in the circulation. In pathological conditions related to an increase in acellular Hb in circulation, NO-np are able to prevent negative cardiovascular reactions related to NO scavenging by the acellular Hb. Furthermore, the NO-np are capable of preventing the cardiovascular collapse related to decrease in NO generation after severe hemorrhage without fluid resuscitation. These implications suggest that NO release from NO-np is advantageous over other NO-releasing compounds, because it does not depend on chemical decomposition or enzymatic catalysis. On the basis of the observed physiological properties, NO-np has clear potential as a therapeutic agent and as a research tool to increase our understanding of NO signaling mechanisms within the cardiovascular system.