A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease

作者：Pritchard Manon F; Powell Lydia C; Menzies Georgina E; Lewis Paul D; Hawkins Karl; Wright Chris; Doull Iolo; Walsh Timothy R; Onsoyen Edvar; Dessen Arne; Myrvold Rolf; Rye Philip D; Myrset Astrid H; Stevens Howard N E; Hodges Lee A; MacGregor Gordon; Neilly James B; Hill Katja E; Thomas David W

来源：Molecular Pharmaceutics, 2016, 13(3): 863-872.

DOI：10.1021/acs.molpharmaceut.5b00794

• mucin
• sputum
• polymer therapy
• alginate
• cystic fibrosis
• viscoelasticity
• safety

The host- and bacteria-derived extracellular polysiccharide 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. Human studies 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.

• 出版日期2016-3