Journal
MOLECULAR PHARMACEUTICS
Volume 13, Issue 3, Pages 863-872Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.5b00794
Keywords
mucin; sputum; polymer therapy; alginate; cystic fibrosis; viscoelasticity; safety
Funding
- European Union via the Eurostars Programme
- European Union via the European Social Fund
- Research Council of Norway
- Cystic Fibrosis Foundation US
- AlgiPharma AS
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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.
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