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Pritchard MF, Powell LC, Menzies GE, et al. A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease. Mol Pharm. 2016;13(3):863-72doi: 10.1021/acs.molpharmaceut.5b00794.
Pritchard, M. F., Powell, L. C., Menzies, G. E., Lewis, P. D., Hawkins, K., Wright, C., Doull, I., Walsh, T. R., Onsøyen, E., Dessen, A., Myrvold, R., Rye, P. D., Myrset, A. H., Stevens, H. N., Hodges, L. A., MacGregor, G., Neilly, J. B., Hill, K. E., & Thomas, D. W. (2016). A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease. Molecular pharmaceutics, 13(3), 863-72. https://doi.org/10.1021/acs.molpharmaceut.5b00794
Pritchard, Manon F, et al. "A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease." Molecular pharmaceutics vol. 13,3 (2016): 863-72. doi: https://doi.org/10.1021/acs.molpharmaceut.5b00794
Pritchard MF, Powell LC, Menzies GE, Lewis PD, Hawkins K, Wright C, Doull I, Walsh TR, Onsøyen E, Dessen A, Myrvold R, Rye PD, Myrset AH, Stevens HN, Hodges LA, MacGregor G, Neilly JB, Hill KE, Thomas DW. A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease. Mol Pharm. 2016 Mar 07;13(3):863-72. doi: 10.1021/acs.molpharmaceut.5b00794. Epub 2016 Feb 16. PMID: 26833139.
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Mol Pharm. 2016 Mar 07;13(3):863-72. doi: 10.1021/acs.molpharmaceut.5b00794. Epub 2016 Feb 16.

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

Molecular pharmaceutics

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

Affiliations

  1. Advanced Therapies Group, School of Dentistry, Cardiff University , Cardiff CF14 4XY, U.K.
  2. Respiratory/Cystic Fibrosis Unit, Children's Hospital for Wales , Cardiff CF14 4XW, U.K.
  3. Medical Microbiology, School of Medicine, College of Biomedical and Life Sciences, Cardiff University , Cardiff CF14 4EP, U.K.
  4. AlgiPharma AS, Sandvika 1337, Norway.
  5. Bio-Images Drug Delivery Ltd., Glasgow G4 0SF, U.K.
  6. Gartnavel Hospital, Glasgow G12 0YN, U.K.
  7. Glasgow Royal Infirmary, Glasgow G4 0ET, U.K.

PMID: 26833139 DOI: 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, 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.

Keywords: alginate; cystic fibrosis; mucin; polymer therapy; safety; sputum; viscoelasticity

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