Cystic fibrosis (CF) is an inherited autosomal disease that causes a deficiency in chloride secretion, resulting in thickened respiratory mucus which ultimately disrupts mucociliary clearance and the removal of pathogenic bacteria. Overtime, a thick, stagnant mucus layer accumulates, obstructing airways and provides a suitable environment for bacteria colonization. Nitric oxide (NO), an endogenously produced gas with integral roles in the mammalian immune response to foreign pathogens, holds promise as a CF therapeutic. To effectively develop NO’s utility as a therapeutic agent, the use of NO delivery scaffolds capable of storing and releasing NO under specific environmental conditions has been utilized. While the activity of NO-releasing antibacterial agents have been well documented, its impact on mucus rheology remains unknown. Herein, we evaluated the effects of NO-releasing alginates on the viscoelastic properties of human bronchial epithelial mucus using parallel plate rheology. Secondary amine modified-alginates were selected as the biopolymer scaffold for NO storage and release due to favorable biocompatibility and biodegradability. In addition, these polymers allowed for tunable NO totals and release kinetics dependent on the precursor amine structure. The effect of NO-release kinetics and select scaffold properties (e.g., molecular weight) on mucus rheology will be described.

Efficacy of nitric oxide-releasing alginates for improving mucus rheology

254th National Meeting (2017)

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