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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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