| Literature DB >> 26833139 |
Manon F Pritchard1, Lydia C Powell1, Georgina E Menzies, Paul D Lewis, Karl Hawkins, Chris Wright, Iolo Doull2, Timothy R Walsh3, Edvar Onsøyen4, Arne Dessen4, Rolf Myrvold4, Philip D Rye4, Astrid H Myrset4, Howard N E Stevens5, Lee A Hodges5, Gordon MacGregor6, James B Neilly7, Katja E Hill1, David W Thomas1.
Abstract
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.Entities:
Keywords: alginate; cystic fibrosis; mucin; polymer therapy; safety; sputum; viscoelasticity
Mesh：
Substances：
Year: 2016 PMID： 26833139 DOI： 10.1021/acs.molpharmaceut.5b00794
Source DB: PubMed Journal: Mol Pharm ISSN： 1543-8384 Impact factor: 4.939