Springe direkt zu Inhalt

661. Thiolated polyglycerol sulfate as potential mucolytic for muco- obstructive lung diseases

J. Arenhoevel, A. Kuppe, A. Addante, L.-F. Wei, N. Boback, C. Butnarasu, Y. Zhong, C. Wong, S. Y. Graeber, J. Duerr, M. Gradzielski, D. Lauster, M. A. Mall, R. Haag – 2024

Increased disulfide crosslinking of secreted mucins causes elevated viscoelasticity of mucus and is a key determinant of mucus dysfunction in patients with cystic fibrosis (CF) and other muco-obstructive lung diseases. In this study, we describe the synthesis of a novel thiol-containing, sulfated dendritic polyglycerol (dPGS-SH), designed to chemically reduce these abnormal crosslinks, which we demonstrate with mucolytic activity assays in sputum from patients with CF. This mucolytic polymer, which is based on a reportedly anti-inflammatory polysulfate scaffold, additionally carries multiple thiol groups for mucolytic activity and can be produced on a gram-scale. After a physicochemical compound characterization, we compare the mucolytic activity of dPGS-SH to the clinically approved N-acetylcysteine (NAC) using Western blot studies and investigate the effect of dPGS-SH on the viscoelastic properties of sputum samples from CF patients by oscillatory rheology. We show that dPGS-SH is more effective than NAC in reducing multimer intensity of the secreted mucins MUC5B and MUC5AC and demonstrate significant mucolytic activity by rheology. In addition, we provide data for dPGS-SH demonstrating a high compound stability, low cytotoxicity, and superior reaction kinetics over NAC at different pH levels. Our data support further development of the novel reducing polymer system dPGS-SH as a potential mucolytic to improve mucus function and clearance in patients with CF as well as other muco-obstructive lung diseases.

Title
661. Thiolated polyglycerol sulfate as potential mucolytic for muco- obstructive lung diseases
Author
J. Arenhoevel, A. Kuppe, A. Addante, L.-F. Wei, N. Boback, C. Butnarasu, Y. Zhong, C. Wong, S. Y. Graeber, J. Duerr, M. Gradzielski, D. Lauster, M. A. Mall, R. Haag
Date
2024
Identifier
DOI: 10.1039/D4BM00381K
Source(s)
Citation
Biomater. Sci., 2024, in press
Type
Text