The purpose of the research being proposed is to develop a highly effective nasal rinse that can treat chronic rhinosinusitis (CRS) in an entirely new way. Often CRS is overlooked because it is rarely life- threatening. CRS is estimated to affect an astounding 13% of the US population with direct costs exceeding $8 billion annually, and additionally causing 73 million limited activity days according to the 1992 CDC Vital and Health Statistics report. Coupling said impact with a lack of effective therapies creates a strong opportunity to address a major unmet need in the market. Many individuals suffering from CRS exhibit decrease nitric oxide (NO) concentrations in their sinus cavities. NO is a potent and natural antimicrobial molecule that healthy individuals produce at high levels in their sinuses. NOTA Laboratories, LLC, has identified safe and naturally occurring therapeutic agents that can enhance the levels of NO in the sinus airways. NO has been proven to stimulate mucociliary clearance and reduces microbial biofilm formation. Dr. Meyerhoff's laboratory at the University of Michigan has spent >15 years studying the biomedical applications of NO releasing agents/materials and has worked with several outside parties to harness the therapeutic properties of NO in the healthcare space. NOTA Laboratories' team of researchers, chemists, pulmonologists, and otolaryngologists believes in this innovative therapy, and has the expertise to further its development to treat/prevent CRS. Using funding from this NIH STTR, the company plans to 1) identify and optimize a formulation that incorporates S-nitrosoglutathione (GSNO) along with additives within typical saline sinus rinse solutions and examine the rates of NO release at room temperature and 37 oC using chemiluminescence measurements; and 2) test the ability of such NO-releasing solutions to disrupt bacterial biofilm, kill biofilm bacteriaand increase ciliary beat frequency in vitro using biofilms established on mucociliary- differentiated primary sinus epithelial cell cultures. The results will drive Phase II studies where NOTA will tes the optimal nasal rinse formulations derived from this Phase I study in suitable animal models as a prelude to clinical trials in collaboration with a research team at the University of Michigan Medical School.