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A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease / Manon F. Pritchard, Lydia C. Powell, Georgina Menzies, Paul Lewis, Karl Hawkins, Chris Wright, Iolo Doull, Timothy R. Walsh, Edvar Onsøyen, Arne Dessen, Rolf Myrvold, Philip D. Rye, Astrid H. Myrset, Howard N. E. Stevens, Lee A. Hodges, Gordon MacGregor, James B. Neilly, Katja E. Hill, David W. Thomas, Christopher Wright
Molecular Pharmaceutics, Volume: 13, Issue: 3, Pages: 863 - 872
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The host- and bacteria-derived extracellular polysaccharide coating of the lung is a considerable challenge in chronic respiratory disease and is a powerful barrier to effective drug delivery. A low molecular weight 12–15-mer alginate oligosaccharide (OligoG CF-5/20), derived from plant biopolymers,...
|Published in:||Molecular Pharmaceutics|
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The host- and bacteria-derived extracellular polysaccharide coating of the lung is a considerable challenge in chronic respiratory disease and is a powerful barrier to effective drug delivery. A low molecular weight 12–15-mer alginate oligosaccharide (OligoG CF-5/20), derived from plant biopolymers, was shown to modulate the polyanionic components of this coating. Molecular modeling and Fourier transform infrared spectroscopy demonstrated binding between OligoG CF-5/20 and respiratory mucins. Ex vivo studies showed binding induced alterations in mucin surface charge and porosity of the three-dimensional mucin networks in cystic fibrosis (CF) sputum. Studies in Humans showed that OligoG CF-5/20 is safe for inhalation in CF patients with effective lung deposition and modifies the viscoelasticity of CF-sputum. OligoG CF-5/20 is the first inhaled polymer therapy, represents a novel mechanism of action and therapeutic approach for the treatment of chronic respiratory disease, and is currently in Phase IIb clinical trials for the treatment of CF.
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mucin, sputum, polymer therapy, alginate, cystic fibrosis, viscoelasticity, safety
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