PGSE-NMR and SANS Studies of the Interaction of Model Polymer Therapeutics with Mucin

The viscous mucus coating that adheres to the epithelial surfaces of mammalian organs provides protection for the underlying tissues and is an efficient barrier to drug delivery. Pulsed-gradient spin−echo NMR and small-angle neutron scattering have been used to study the aqueous solution interaction...

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Bibliographic Details
Published in:Biomacromolecules 2010-01, Vol.11 (1), p.120-125
Main Authors: Griffiths, Peter Charles, Occhipinti, Paola, Morris, Christopher, Heenan, Richard K, King, Stephen Michael, Gumbleton, Mark
Format: Article
Language:English
Subjects:
Animals
Applied sciences
Biological and medical sciences
Diffusion
Drug Delivery Systems
Exact sciences and technology
Fundamental and applied biological sciences. Psychology
General pharmacology
In solution. Condensed state. Thin layers
Magnetic Resonance Spectroscopy
Medical sciences
Models, Molecular
Molecular biophysics
Mucins - chemistry
Mucins - metabolism
Neutron Diffraction
Organic polymers
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Physico-chemical properties of biomolecules
Physicochemistry of polymers
Polymers - chemistry
Polymers - metabolism
Properties and characterization
Scattering, Small Angle
Solution and gel properties
Solutions
Swine
Water - chemistry
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Summary:The viscous mucus coating that adheres to the epithelial surfaces of mammalian organs provides protection for the underlying tissues and is an efficient barrier to drug delivery. Pulsed-gradient spin−echo NMR and small-angle neutron scattering have been used to study the aqueous solution interaction of various model polymer therapeutics with mucin, the principle organic component within mucus. Nonionic polymers such as linear and star-branched poly(ethylene oxide) (PEO) and dextrin showed no appreciable interaction with mucin but suffered a moderate retardation in their rate of diffusion through the mucin solution. A strong interaction with mucin was observed for a series of polyamidoamine (PAMAM) dendrimers and hyperbranched poly(ethylene imine) (PEI), which displayed a characteristic pH-dependent profile and led to significant reductions in their rates of diffusion. These observations have implications for the design of optimized polymer therapeutic structures being adopted for the delivery of therapeutic moieties through mucin-rich environments.
ISSN:1525-7797
1526-4602
DOI:10.1021/bm9009667