Reighard Katelyn P, Ehre Camille, Rushton Zachary L, Ahonen Mona Jasmine R, Hill David B, Schoenfisch Mark H
Department of Chemistry, University of North Carolina-Chapel Hill, 131 South Road, Chapel Hill, North Carolina 27599, United States.
Marsico Lung Institute, University of North Carolina-Chapel Hill, 125 Mason Farm Road, Chapel Hill, North Carolina 27599, United States.
ACS Biomater Sci Eng. 2017;3(6):1017-1026. doi: 10.1021/acsbiomaterials.7b00039. Epub 2017 May 15.
Nitric oxide (NO)-releasing chitosan oligosaccharides were modified with ester functional groups to examine how the mucoadhesive nature of the scaffold impacts the ability of NO to degrade mucins from human bronchial epithelial cell cultures and clinical sputum samples collected from patients with cystic fibrosis (CF). Agarose gel electrophoresis experiments indicated that the mucoadhesive NO-releasing chitosan oligosaccharides degraded both the purified mucins and sputum, while control scaffolds (without NO release or mucoadhesive ligands) had no effect on mucin structure. Microscopic observations of sputum treated with the mucoadhesive NO-releasing chitosan oligosaccharide confirmed degradation of the mucin and DNA networks. Similarly, the viscosity and elasticity of sputum were reduced upon treatment with the mucoadhesive NO-releasing chitosan, demonstrating the potential utility of these NO-releasing scaffolds as mucolytic agents.
用酯官能团修饰释放一氧化氮(NO)的壳寡糖,以研究支架的黏膜黏附特性如何影响NO从人支气管上皮细胞培养物和从囊性纤维化(CF)患者收集的临床痰液样本中降解黏蛋白的能力。琼脂糖凝胶电泳实验表明,具有黏膜黏附性的释放NO的壳寡糖可降解纯化的黏蛋白和痰液,而对照支架(不释放NO或无黏膜黏附配体)对黏蛋白结构无影响。对用具有黏膜黏附性的释放NO的壳寡糖处理的痰液进行显微镜观察,证实了黏蛋白和DNA网络的降解。同样,用具有黏膜黏附性的释放NO的壳聚糖处理后,痰液的黏度和弹性降低,证明了这些释放NO的支架作为黏液溶解剂的潜在用途。