Nitric Oxide-Releasing Alginates as Mucolytic Agents

The excessive production of thick, viscous mucus in severe respiratory diseases leads to obstruction of the airways and provides a suitable environment for the colonization of pathogenic bacteria. The effect of nitric oxide (NO)-releasing alginates with varying NO release kinetics on the viscoelastic properties of human bronchial epithelial (HBE) mucus was evaluated as a function of the NO-release kinetics using parallel plate rheology. Low-molecular-weight (∼5 kDa) alginates with high NO flux (∼4000 ppb/mg) and sustained release (half-life ∼0.3 h) proved to be most effective in reducing both mucus elasticity and viscosity (≥60% reduction for both). The efficacy of the NO-releasing alginates was shown to be dose-dependent, with high concentrations of NO-releasing alginates (∼80 mg·mL–1) resulting in greater reduction of the viscosity and elasticity of the mucus samples. Greater reduction in mucus rheology was also achieved with NO-releasing alginates at lower concentrations when compared with both NO-releasing chitosan, a similarly biocompatible cationic polymer, and N-acetyl cysteine (NAC), a conventional mucolytic agent.