Ahonen Mona Jasmine R, Hill David B, Schoenfisch Mark H
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290, United States.
Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7248, United States.
ACS Biomater Sci Eng. 2019 Jul 8;5(7):3409-3418. doi: 10.1021/acsbiomaterials.9b00482. Epub 2019 May 24.
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) 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 acetyl cysteine (NAC), a conventional mucolytic agent.
在严重的呼吸道疾病中，浓稠、粘性的黏液过度产生会导致气道阻塞，并为病原菌的定植提供适宜的环境。使用平行板流变学方法，研究了具有不同一氧化氮（NO）释放动力学的NO释放藻酸盐对人支气管上皮（HBE）黏液粘弹性的影响，并将其作为NO释放动力学的函数进行评估。低分子量（约5 kDa）、高NO通量（约4000 ppb/mg）和持续释放（半衰期约0.3小时）的藻酸盐在降低黏液弹性和黏度方面最为有效（两者均降低≥60%）。NO释放藻酸盐的疗效呈剂量依赖性，高浓度的NO释放藻酸盐（约80 mg•mL）可使黏液样品的黏度和弹性有更大程度的降低。与同样具有生物相容性的阳离子聚合物NO释放壳聚糖和传统黏液溶解剂乙酰半胱氨酸（NAC）相比，较低浓度的NO释放藻酸盐也能使黏液流变学有更大程度的降低。
