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

Lydia Powell Orcid Logo, Manon F. Pritchard, Lydia C. Powell, Georgina Menzies Orcid Logo, Paul Lewis, Karl Hawkins Orcid Logo, 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 Orcid Logo

Molecular Pharmaceutics, Volume: 13, Issue: 3, Pages: 863 - 872

Swansea University Authors: Lydia Powell Orcid Logo, Georgina Menzies Orcid Logo, Paul Lewis, Karl Hawkins Orcid Logo, Christopher Wright Orcid Logo

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DOI (Published version): 10.1021/acs.molpharmaceut.5b00794

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,...

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Published in: Molecular Pharmaceutics
ISSN: 1543-8384 1543-8392
Published: 2016
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URI: https://cronfa.swan.ac.uk/Record/cronfa26822
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A low molecular weight 12&#x2013;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.</abstract><type>Journal Article</type><journal>Molecular Pharmaceutics</journal><volume>13</volume><journalNumber>3</journalNumber><paginationStart>863</paginationStart><paginationEnd>872</paginationEnd><publisher/><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>1543-8384</issnPrint><issnElectronic>1543-8392</issnElectronic><keywords>mucin, sputum, polymer therapy, alginate, cystic fibrosis, viscoelasticity, safety</keywords><publishedDay>1</publishedDay><publishedMonth>2</publishedMonth><publishedYear>2016</publishedYear><publishedDate>2016-02-01</publishedDate><doi>10.1021/acs.molpharmaceut.5b00794</doi><url/><notes>ACS AuthorChoice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.</notes><college>COLLEGE NANME</college><department>Biomedical Sciences</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>BMS</DepartmentCode><institution>Swansea University</institution><apcterm/><lastEdited>2020-12-11T09:51:21.0950143</lastEdited><Created>2016-03-21T13:15:26.0531145</Created><path><level id="1">Faculty of Science and Engineering</level><level id="2">School of Engineering and Applied Sciences - Biomedical Engineering</level></path><authors><author><firstname>Lydia</firstname><surname>Powell</surname><orcid>0000-0002-8641-0160</orcid><order>1</order></author><author><firstname>Manon F.</firstname><surname>Pritchard</surname><order>2</order></author><author><firstname>Lydia C.</firstname><surname>Powell</surname><order>3</order></author><author><firstname>Georgina</firstname><surname>Menzies</surname><orcid>0000-0002-6600-6507</orcid><order>4</order></author><author><firstname>Paul</firstname><surname>Lewis</surname><order>5</order></author><author><firstname>Karl</firstname><surname>Hawkins</surname><orcid>0000-0003-0174-4151</orcid><order>6</order></author><author><firstname>Chris</firstname><surname>Wright</surname><order>7</order></author><author><firstname>Iolo</firstname><surname>Doull</surname><order>8</order></author><author><firstname>Timothy R.</firstname><surname>Walsh</surname><order>9</order></author><author><firstname>Edvar</firstname><surname>Ons&#xF8;yen</surname><order>10</order></author><author><firstname>Arne</firstname><surname>Dessen</surname><order>11</order></author><author><firstname>Rolf</firstname><surname>Myrvold</surname><order>12</order></author><author><firstname>Philip D.</firstname><surname>Rye</surname><order>13</order></author><author><firstname>Astrid H.</firstname><surname>Myrset</surname><order>14</order></author><author><firstname>Howard N. 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spelling 2020-12-11T09:51:21.0950143 v2 26822 2016-03-21 A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease 0e7e702952672bcbfdfd4974199202fb 0000-0002-8641-0160 Lydia Powell Lydia Powell true false 6db82d349cf11c9596217afe9228e1c3 0000-0002-6600-6507 Georgina Menzies Georgina Menzies true false 46dfc22d7468f247c390ba0c6cd8fba6 Paul Lewis Paul Lewis true false 77c39404a9a98c6e2283d84815cba053 0000-0003-0174-4151 Karl Hawkins Karl Hawkins true false 235e125ac3463e2ee7fc98604bf879ce 0000-0003-2375-8159 Christopher Wright Christopher Wright true false 2016-03-21 BMS 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. Journal Article Molecular Pharmaceutics 13 3 863 872 1543-8384 1543-8392 mucin, sputum, polymer therapy, alginate, cystic fibrosis, viscoelasticity, safety 1 2 2016 2016-02-01 10.1021/acs.molpharmaceut.5b00794 ACS AuthorChoice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2020-12-11T09:51:21.0950143 2016-03-21T13:15:26.0531145 Faculty of Science and Engineering School of Engineering and Applied Sciences - Biomedical Engineering Lydia Powell 0000-0002-8641-0160 1 Manon F. Pritchard 2 Lydia C. Powell 3 Georgina Menzies 0000-0002-6600-6507 4 Paul Lewis 5 Karl Hawkins 0000-0003-0174-4151 6 Chris Wright 7 Iolo Doull 8 Timothy R. Walsh 9 Edvar Onsøyen 10 Arne Dessen 11 Rolf Myrvold 12 Philip D. Rye 13 Astrid H. Myrset 14 Howard N. E. Stevens 15 Lee A. Hodges 16 Gordon MacGregor 17 James B. Neilly 18 Katja E. Hill 19 David W. Thomas 20 Christopher Wright 0000-0003-2375-8159 21 0026822-22072016101113.pdf Pritchard2016.pdf 2016-07-22T10:11:13.5030000 Output 6073809 application/pdf Version of Record true 2016-07-22T00:00:00.0000000 false
title A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease
spellingShingle A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease
Lydia Powell
Georgina Menzies
Paul Lewis
Karl Hawkins
Christopher Wright
title_short A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease
title_full A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease
title_fullStr A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease
title_full_unstemmed A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease
title_sort A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease
author_id_str_mv 0e7e702952672bcbfdfd4974199202fb
6db82d349cf11c9596217afe9228e1c3
46dfc22d7468f247c390ba0c6cd8fba6
77c39404a9a98c6e2283d84815cba053
235e125ac3463e2ee7fc98604bf879ce
author_id_fullname_str_mv 0e7e702952672bcbfdfd4974199202fb_***_Lydia Powell
6db82d349cf11c9596217afe9228e1c3_***_Georgina Menzies
46dfc22d7468f247c390ba0c6cd8fba6_***_Paul Lewis
77c39404a9a98c6e2283d84815cba053_***_Karl Hawkins
235e125ac3463e2ee7fc98604bf879ce_***_Christopher Wright
author Lydia Powell
Georgina Menzies
Paul Lewis
Karl Hawkins
Christopher Wright
author2 Lydia Powell
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
format Journal article
container_title Molecular Pharmaceutics
container_volume 13
container_issue 3
container_start_page 863
publishDate 2016
institution Swansea University
issn 1543-8384
1543-8392
doi_str_mv 10.1021/acs.molpharmaceut.5b00794
college_str Faculty of Science and Engineering
hierarchytype
hierarchy_top_id facultyofscienceandengineering
hierarchy_top_title Faculty of Science and Engineering
hierarchy_parent_id facultyofscienceandengineering
hierarchy_parent_title Faculty of Science and Engineering
department_str School of Engineering and Applied Sciences - Biomedical Engineering{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Engineering and Applied Sciences - Biomedical Engineering
document_store_str 1
active_str 0
description 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.
published_date 2016-02-01T03:32:19Z
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score 11.037056

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