Disruption of Pseudomonas aeruginosa biofilms using a novel nitric oxide-releasing nanoparticle

P.I.: Waleed Abuzeid, MD
Associate Professor, Medicine, Otolaryngology

Nearly all patients with cystic fibrosis (CF) develop chronic rhinosinusitis (CRS) which can have a significant impact on quality-of-life. A consequence of CRS in CF patients may include more frequent pulmonary exacerbations. The pathophysiology of CF-related CRS often involves the development of Pseudomonas aeruginosa (PA) biofilms. The rabbit model of sinusitis has been established in prior studies. However, it has not been exploited to investigate chronic infection caused by CF-relevant strains of PA. We hypothesize that CF related PA strains will cause sinusitis by readily growing in the maxillary sinus of New Zealand white rabbits, eventually forming biofilms and inducing an epithelial inflammatory response.

Biofilms are inherently resistant to conventional antibiotics and have been associated with disease recalcitrance in CRS. Nitric oxide (NO) is a key component of the innate immune system with antibiofilm effects. We have previously demonstrated sustained release of NO from a nanoparticle (NO-NP) that induced a >80% reduction in cell volume and viability in biofilms grown from several clinical PA strains. The rabbit model of sinusitis is an optimal platform on which to evaluate NO-NP efficacy and toxicity. We hypothesize that NO-NP will produce a significant reduction in PAO1 biofilms without epithelial toxicity in the rabbit model.