| Autor: |
Mansfield ED; School of Pharmacy, University of Reading, Whiteknights, Reading, Berkshire RG6 6AD, UK. v.khutoryanskiy@reading.ac.uk., de la Rosa VR; Supramolecular Chemistry Group, Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281 S4, B-9000, Ghent, Belgium. Richard.hoogenboom@ugent.be., Kowalczyk RM; Chemical Analysis Facility, University of Reading, Whiteknights, Reading, Berkshire RG6 6AD, UK., Grillo I; Institut Laue-Langevin, 71 avenue des Martyrs, 38000 Grenoble, France., Hoogenboom R; Supramolecular Chemistry Group, Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281 S4, B-9000, Ghent, Belgium. Richard.hoogenboom@ugent.be., Sillence K; Malvern Instruments Limited, London Road, Minton Park, Amesbury, Wiltshire SP4 7RT, UK., Hole P; Malvern Instruments Limited, London Road, Minton Park, Amesbury, Wiltshire SP4 7RT, UK., Williams AC; School of Pharmacy, University of Reading, Whiteknights, Reading, Berkshire RG6 6AD, UK. v.khutoryanskiy@reading.ac.uk., Khutoryanskiy VV; School of Pharmacy, University of Reading, Whiteknights, Reading, Berkshire RG6 6AD, UK. v.khutoryanskiy@reading.ac.uk. |
| Abstrakt: |
Functionalised nanomaterials are gaining popularity for use as drug delivery vehicles and, in particular, mucus penetrating nanoparticles may improve drug bioavailability via the oral route. To date, few polymers have been investigated for their muco-penetration, and the effects of systematic structural changes to polymer architectures on the penetration and diffusion of functionalised nanomaterials through mucosal tissue have not been reported. We investigated the influence of poly(2-oxazoline) alkyl side chain length on nanoparticle diffusion; poly(2-methyl-2-oxazoline), poly(2-ethyl-2-oxazoline), and poly(2-n-propyl-2-oxazoline) were grafted onto the surface of thiolated silica nanoparticles and characterised by FT-IR, Raman and NMR spectroscopy, thermogravimetric analysis, and small angle neutron scattering. Diffusion coefficients were determined in water and in a mucin dispersion (using Nanoparticle Tracking Analysis), and penetration through a mucosal barrier was assessed using an ex vivo fluorescence technique. The addition of a single methylene group in the side chain significantly altered the penetration and diffusion of the materials in both mucin dispersions and mucosal tissue. Nanoparticles functionalised with poly(2-methyl-2-oxazoline) were significantly more diffusive than particles with poly(2-ethyl-2-oxazoline) while particles with poly(2-n-propyl-2-oxazoline) showed no significant increase compared to the unfunctionalised particles. These data show that variations in the polymer structure can radically alter their diffusive properties with clear implications for the future design of mucus penetrating systems. |
