title: PGSE-NMR and SANS studies of the interaction of model polymer therapeutics with mucin.
abstract: 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.
authors: School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff CF10 3AT, United Kingdom. griffithspc@cardiff.ac.uk
authors: Peter Charles
authors: PC
authors: Griffiths
authors: Paola
authors: P
authors: Occhipinti
authors: Christopher
authors: C
authors: Morris
authors: Richard K
authors: RK
authors: Heenan
authors: Stephen Michael
authors: SM
authors: King
authors: Mark
authors: M
authors: Gumbleton
mesh_terms: D000818:Animals; D004058:Diffusion; D016503:Drug Delivery Systems; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009077:Mucins / Q000737:chemistry / Q000378:metabolism*; D033363:Neutron Diffraction; D011108:Polymers / Q000737:chemistry / Q000378:metabolism*; D053838:Scattering, Small Angle; D012996:Solutions; D013552:Swine; D014867:Water / Q000737:chemistry*
chemical_list: D009077:Mucins; D011108:Polymers; D012996:Solutions; D014867:Water