Side chain variations radically alter the diffusion of poly(2-alkyl-2-oxazoline) functionalised nanoparticles through a mucosal barrier (original) (raw)
* Corresponding authors
a School of Pharmacy, University of Reading, Whiteknights, Reading, Berkshire, UK
E-mail: v.khutoryanskiy@reading.ac.uk
b Supramolecular Chemistry Group, Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281 S4, Ghent, Belgium
E-mail: Richard.hoogenboom@ugent.be
c Chemical Analysis Facility, University of Reading, Whiteknights, Reading, Berkshire, UK
d Institut Laue-Langevin, 71 avenue des Martyrs, 38000 Grenoble, France
e Malvern Instruments Limited, London Road, Minton Park, Amesbury, Wiltshire, UK
Abstract
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.
- This article is part of the themed collection:Open access articles from Biomaterials Science
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Article information
DOI
https://doi.org/10.1039/C6BM00375C
Article type
Paper
Submitted
03 Jun 2016
Accepted
05 Jul 2016
First published
11 Jul 2016
This article is Open Access
Download Citation
Biomater. Sci., 2016,4, 1318-1327
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Side chain variations radically alter the diffusion of poly(2-alkyl-2-oxazoline) functionalised nanoparticles through a mucosal barrier
E. D. H. Mansfield, V. R. de la Rosa, R. M. Kowalczyk, I. Grillo, R. Hoogenboom, K. Sillence, P. Hole, A. C. Williams and V. V. Khutoryanskiy,Biomater. Sci., 2016, 4, 1318DOI: 10.1039/C6BM00375C
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