Development and optimization of a nitric oxide releasing microparticle formulation for the topical treatment of chronic rhinosinusitis - chronic rhinosinusitis (CRS), defined by persistent…

The National Institute of Allergy and Infectious Diseases awarded $600,000 to Zylo Therapeutics, Inc. on September 12, 2025, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop and optimize a nitric oxide-releasing microparticle formulation for topical treatment of chronic rhinosinusitis.

Chronic rhinosinusitis, characterized by persistent inflammation and infection of the nasal cavity and paranasal sinuses, affects approximately 13 million U.S. adults. Treatment-resistant cases often involve bacterial biofilms that exhibit 10- to 1,000-fold higher antimicrobial resistance than planktonic bacteria and are associated with worse symptom scores, recurrent infections, increased need for surgical intervention, and poorer surgical outcomes. Conventional antibiotics frequently require clinically unsafe dose increases; topical treatments demonstrate only short-term efficacy. The project addresses this unmet therapeutic need through synthesis and characterization of a nitric oxide-releasing microparticle formulation designed to overcome biofilm-mediated treatment resistance.

Zylo Therapeutics, a self-certified small disadvantaged business located in Greenville, South Carolina, specializes in microparticle-based topical drug delivery systems. The award period extends from September 12, 2025, through August 31, 2027, with performance at the Greenville location. The project is structured around two interconnected specific aims focused on clinical translation and optimization of the microparticle formulation.

Development and optimization of a nitric oxide releasing microparticle formulation for the topical treatment of chronic rhinosinusitis - chronic rhinosinusitis (CRS), defined by persistent inflammation and/or infection of the nasal cavity and paranasal sinuses, has a prevalence of 3.6% in the united states adult population, equating to approximately 13 million affected individuals.1,2 symptoms include nasal obstruction, facial pressure, nasal drainage, and hyposmia.3,4 bacteria implicated in the pathogenesis of CRS can form biofilms, which are communities of bacteria that coordinate behavior through quorum sensing-a cell density-dependent signal transduction process-to proliferate.25 increasing evidence suggests that biofilms play an important role in the etiology and morbidity of CRS.26-30 gram-negative organisms, including PA, are potent biofilm formers and are frequently observed in treatment-resistant CRS.31,35,36 biofilms, in contrast to planktonic bacteria, harbor unique characteristics that imbue them with a 10-1000 fold higher resistance to antimicrobials. In an evaluation of patients with medially recalcitrant CRS, biofilms were associated with: (I) worse CRS symptom score, (II) worse radiologic appearance, (III) recurrent infections, (IV) increased need for surgical intervention, and (V) in those undergoing sinus surgery, poorer surgical outcomes versus non-biofilm CRS.41-43 in many cases, treatment using conventional antibiotics would require a 60-1,000-fold increase in dose, which would be clinically unsafe.44 topical antibiotic treatment, such as mupirocin nasal irrigations, can be more effective in biofilm treatment, but have demonstrated only short-term efficacy.45,46 consequently, there is a pressing need for more effective antibacterial therapies in CRS. The goal of this proposal will be achieved through two interconnected specific aims. Specific aim 1: for clinical-translation purposes, ZMP-no.2 will be synthesized and characterized prior to being evaluated for in vitro antibacterial activity against P. Aeruginosa and other bacterial strains relevant to CRS as well as for preliminary cytotoxicity. Specific aim 2: the concentrations of ZMP-no.2 in a GEL vehicle required to deliver sufficient no to the sinus epithelial tissues to achieve bactericidal activity will be established; this formulation will then be used to assess ZMP-no.2 efficacy in treating P. Aeruginosa in a rabbit in vivo sinusitis model. At the conclusion of this phase 1 study, an optimized test formulation will be established with a defined concentration of ZMP-no.2 suitable for further formulation development, scale-up, safety studies, and EX vivo efficacy studies in phase 2.