Thiolated polyglycerol sulfate as potential mucolytic for muco-obstructive lung diseases.
Biomater Sci
; 12(17): 4376-4385, 2024 Aug 20.
Article
in En
| MEDLINE
| ID: mdl-39028033
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polymers
/
Sputum
/
Sulfhydryl Compounds
/
Glycerol
Limits:
Humans
Language:
En
Journal:
Biomater Sci
Year:
2024
Document type:
Article
Affiliation country:
Germany
Country of publication:
United kingdom