NO tablet: autonomous generation of therapeutic nitric oxide in air through redox-promoted CO2 adsorption

Inhaled nitric oxide (iNO) is a powerful therapy for the treatment of various cardiopulmonary and respiratory diseases. However, access to iNO therapy is often limited by the necessity of cumbersome gas tanks and/or elaborate gas blending apparatus. Here, we report a lightweight, inexpensive, and maintenance-free tablet that autonomously generates a therapeutic quantity of NO in air. The tablet is composed of a thimble filter paper containing a powdery mixture of nitrite (NO2‒)-type layered double hydroxide (NLDH) and ascorbic acid loaded on silica gel (AASiO2). NLDH by itself generates trace amounts of NO in the air due to the left-shifting of the protonation equilibrium of NO2‒ by aerial CO2 and H2O (2[NO2‒]LDH + CO2 + H2O ⇌ 2HNO2↑ + [CO32‒]LDH), which is followed by disproportionation of 2HNO2 to NO, NO2 and H2O. In contrast, it was found that the protonation equilibrium can be shifted to the right side when volatile acid products (HNO2 and NO2) are readily converted to neutral NO over the AASiO2 reductant. Based on this, even a single tablet (containing 0.30 g NLDH and 0.90 g AASiO2) generates 5~20 ppm NO at 0.5 L/min for 24 h, which is sufficient to be useful for the relief of severe hypoxia caused by persistent pulmonary hypertension of the newborn (PPHN). Moreover, the tablet can be activated by exhaled breath for high-dose iNO therapy (80~180 ppm for several hours), revealing its potential utility for treating viral pneumonia. The NO tablet can be stored stably over long periods at ambient temperature in a gas barrier bag, and has the potential to break the logistical, financial, and operational barriers that have long existed to the widespread implementation of iNO therapy.