Inhalable Nitric Oxide Delivery Systems for Pulmonary Arterial Hypertension Treatment

Abstract

Pulmonary arterial hypertension (PAH) is a severe medical condition characterized by elevated blood pressure in the pulmonary arteries. Nitric oxide (NO) is a gaseous signaling molecule with potent vasodilator effects; however, inhaled NO is limited in clinical practice because of the need for tracheal intubation and the toxicity of high NO concentrations. In this study, inhalable NO-releasing microspheres (NO inhalers) are fabricated to deliver nanomolar NO through a nebulizer. Two NO inhalers with distinct porous structures are prepared depending on the molecular weights of NO donors. It is confirmed that pore formation can be controlled by regulating the migration of water molecules from the external aqueous phase to the internal aqueous phase. Notably, open porous NO inhalers (OPNIs) can deliver NO deep into the lungs through a nebulizer. Furthermore, OPNIs exhibit vasodilatory and anti-inflammatory effects via sustained NO release. In conclusion, the findings suggest that OPNIs with highly porous structures have the potential to serve as tools for PAH treatment. For easy and safe pulmonary arterial hypertension (PAH) treatment, open porous nitric oxide (NO) inhalers (OPNIs) with efficient pulmonary delivery and sustained NO release properties are synthesized through the increased migration of water molecules during the preparation processes. The OPNIs demonstrate therapeutic effects on PAH by promoting cyclic guanosine monophosphate synthesis in smooth muscle cells and modulating macrophage polarization.image