Abstract:
Nitric oxide (NO) plays a critical role in a wide range of bodily functions, including vasodilation,
neurotransmission, wound healing, suppression of platelet activation, and modulation of ciliary beat frequency.
In addition, it is a potent and endogenous antimicrobial/antiviral agent produced by macrophages and normally
present at moderate levels (0.20-1.0 ppmv) within the upper airways/sinuses of healthy individuals to help
prevent chronic upper airway infections. It has been found that significant suppression of NO levels occurs in
patients suffering from chronic rhinosinusitis (CRS), and difficult-to-treat lower respiratory infections associated
with chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). Consequently, it has been shown
that patients with respiratory maladies benefit greatly from inhaled nitric oxide (iNO) therapy. In addition, iNO
at higher levels (10-50 ppmv) is routinely used in the hospital setting to treat newborns with pulmonary
hypertension, adults with acute respiratory distress syndrome (ARDS), and patients with of other respiratory
infections such as pneumonia and tuberculosis. Further, it has been demonstrated that iNO therapy improves
reperfusion of brain tissue after a stroke, promotes recovery in liver transplant patients, and prevents systemic
inflammatory response syndrome (SIRS) (when added to the oxygenator sweep gas) in patients that undergo
cardiopulmonary bypass surgery (CPB). Currently, the high cost ($3,000 per day) of iNO delivery systems,
which rely on low NO concentrations in metal gas cylinders, restricts the use of gas phase NO both within and
outside of the hospital setting. Given the wide diversity of applications and the need to deliver NO in various
health care settings (in-patient/out-patient care) and at a much lower cost, there is a growing need for an
inexpensive, portable and simple-to-use system to create gas phase NO on demand.
Working in collaboration with researchers in the Department of Chemistry at the Univ. of Michigan, NOTA
Laboratories proposes to develop such an iNO delivery system. NOTA’s proposed product will consist of a
single use reel-to-reel cartridge containing a roll (5-10 m) of S-nitrosothiol (RSNO), either S-nitroso-N-acetyl-
penicillamine (SNAP) or S-nitroso-glutathione (GSNO), immobilized onto a polymer carrier. The roll of RSNO
film will be housed within a light-resistant compartment and advanced through an illumination zone that is
equipped with several light emitting diodes (LEDs) that produce wavelengths at which NO can be efficiently
photo-released from the RSNO species (380-580 nm). The advancement of the film through the translucent
light compartment will be achieved using a motor-driven pick-up wheel that is controlled through a feedback
loop employing a NO electrochemical gas phase sensor situated in-line within the output air stream. A stream
of humidified air will be pumped through the NO generating chamber, with the LEDs intensity being adjusted
via the feedback loop to release NO into the air stream to provide target concentrations of NO (0.20-200 ppmv).
The NO released will then pass out of the LANOR system into the patient’s nose via cannula nasal tubes or a
nasal mask. Phase I research will focus on the building a prototype device that can accommodate the reel-to-
reel cartridge with an NO2 suppression filter as well as developing the roll of film containing the immobilized
RSNO species. Finally, a demonstration of the prototype device’s ability to deliver pure NO at levels between
1 and 200 ppmv for up to 1 week will be made through control of the film advancement and intensity of the
illumination. Long-term storage stability studies will demonstrate that the immobilized RSNO film is stable under
ambient heat and humidity conditions when stored in an aluminum foil pouch. It is anticipated that the proposed
LANOR system will be able to deliver a broad range of therapeutic iNO levels for at least 1 week, depending
upon the desired NO level and rate of air delivery.
