Nitric Oxide-Releasing Alginates as Mucolytic Agents

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Abstract
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 to both NO-releasing chitosan, a similarly biocompatible cationic polymer, and N-acetyl cysteine (NAC), a conventional mucolytic agent.
Funding Information
  • Division of Mathematical Sciences (DMS 1462992)
  • National Institute of Diabetes and Digestive and Kidney Diseases (5P30DK065988)
  • National Institute of Allergy and Infectious Diseases (AI112029)
  • Cystic Fibrosis Foundation (Bouche15R0, Schoen18G0, Hill16XX0)

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