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

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• 作者：Manon F. Pritchard ; Lydia C. Powell ; Georgina E. Menzies ; Paul D. 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
• 刊名：Molecular Pharmaceutics
• 出版年：2016
• 出版时间：March 7, 2016
• 年：2016
• 卷：13
• 期：3
• 页码：863-872
• 全文大小：618K
• ISSN：1543-8392

文摘

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. 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.