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 controlling ciliary beat frequency.
Indeed, inhaled NO (iNO) at 0.1 – 80 ppmv (typically 20 ppmv) has become a common treatment for newborns
with persistent pulmonary hypertension (PPHN). In addition, NO acts as a potent and endogenous
antimicrobial/antiviral agent that is produced by macrophages and the paranasal sinuses to combat airway
infections. Evidence also exists that NO production is decreased in patients with cystic fibrosis (CF) and chronic
obstructive pulmonary disease (COPD), causing pulmonary hypertension and increased risk of respiratory
infections with bacterial pathogens often forming hard to treat biofilms, as they are are highly resistant to
antibiotics. Because iNO therapy has dual functionality of both pulmonary vasodilation and antimicrobial
activity/biofilm dispersal it is potentially of great benefit to CF and COPD patients. Currently, ongoing clinical
trials are evaluating the efficacy of iNO treatment for CF, COPD, and lower pulmonary infection (bronchiolitis).
Recent research has also demonstrated that iNO therapy improves reperfusion of brain tissue after a stroke and
the heart after infarct. Given the diversity of applications, there is an unmet need for a simple, low-cost and
portable system to deliver iNO therapy beyond the ICU for in-hospital, in-home care and during medical transport.
To meet these emerging needs, NOTA Laboratories proposes to continue development of its proprietary
LANOR™ (Light Activated Nitric Oxide Release) iNO delivery device. Phase II research will focus on producing
two prototypes, a professional model for hospital use and a lower dosing model for patient use at home and for
medical transport. The professional model is intended for use by trained medical staff and will allow higher dosing
and greater flexibility in configuring the system for treatment of a wide variety of diseases and conditions. The
low dose model will ultimately target long-term CF and COPD patient treatment and will prevent user adjustments
to the settings once set as prescribed by the doctor. Both models will use a custom designed I/O PCB board and
significantly shrink the electronics footprint and cost. The preparation of the immobilized S-nitrosothiol (RSNO)
film will be further improved and scaled up by using automated spray and thin-film coating techniques, and the
use of commercial-grade processing equipment. A more advanced replaceable film cartridge design will be
developed using 3D printing and the design will be made into aplastic injection mold. Batches of cGMP-grade
RSNO will be sourced from a chemical manufacturer that uses a cGMP process, and the GSNO will be
immobilized onto a medical grade carrier. The goal for Phase II is to transition the devices into formal
development with implementation of a Quality System that complies with the FDA’s published guidance for
Premarket Notification Submissions for a Nitric Oxide Delivery Apparatus leading to a to an initial 510k
submission for PPHN as this is by far the easiest regulatory path to market.
