Controlled Nitric Oxide Release Using Poly(lactic-co-glycolic acid) Nanoparticles for Anti-Inflammatory Effects

Nitric oxide (NO) plays a key role in several physiological functions such as inflammatory responses and immune regulation. However, despite its beneficial functions, the short half-life and diffusion radius limit NO availability in biomedical applications. Hence, controlled release is important to achieve the desired therapeutic effects with exogenous NO delivery. In this study, we fabricated a poly(lactic-co-glycolic acid) (PLGA)-based NO delivery system to release NO in a sustained manner under physiological conditions. To prevent an initial burst release, branched polyethylenimine diazeniumdiolate (BPEI/NONOate), a pH-responsive NO donor, was encapsulated into the hydrophilic core of PLGA nanoparticles. Furthermore, low concentrations of NO released at a consistent level via a stabilization effect obtained as amine groups of BPEI/NONOate interacted with the nearby NONOate. Using the controlled-release profiles, we successfully regulated the inflammatory response in lipopolysaccharide-stimulated peripheral blood mononuclear cells. This work demonstrates the potential of a NO delivery carrier in the regulation of inflammation.