Mucus-penetrating nanoparticles based on chitosan grafted with various non-ionic polymers: Synthesis, structural characterisation and diffusion studies
[Display omitted] Transmucosal administration offers numerous advantages for drug delivery as it usually helps to avoid first pass metabolism, provides rapid onset of action, and is a non-invasive route. Mucosal surfaces are covered by a viscoelastic mucus gel layer which acts as a protective barrie...
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| Published in: | Journal of colloid and interface science Vol. 626; pp. 251 - 264 |
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| Main Authors: | , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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Elsevier Inc
15-11-2022
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| Abstract | [Display omitted]
Transmucosal administration offers numerous advantages for drug delivery as it usually helps to avoid first pass metabolism, provides rapid onset of action, and is a non-invasive route. Mucosal surfaces are covered by a viscoelastic mucus gel layer which acts as a protective barrier preventing the entrance of harmful substances into the human tissues. This function of mucus also inhibits the diffusion of drugs and nano-formulations and can result in a significant reduction of their efficacy. The design of mucus-penetrating nanoparticles can overcome the barrier function of mucus which may lead to better therapeutic outcomes. In this study, chitosan was chemically modified by grafting short chains of poly(ethylene glycol), poly(2-hydroxyethyl acrylate), poly(2-ethyl-2-oxazoline), or poly(N-vinyl pyrrolidone) and the resulting chitosan derivatives were used to prepare nanoparticles using an ionic gelation method with sodium tripolyphosphate. These nanoparticles were characterised using dynamic light scattering, transmission electron microscopy, small-angle neutron scattering and nanoparticle tracking analysis. Small-angle neutron scattering data revealed the presence of a large amount of water inside these nanoparticles and lack of a heterogeneous internal structure. The nanogel model with low crosslinking density is suggested as the most feasible model to describe the structure of these nanoparticles. The studies of the behaviour of these nanoparticles in bovine submaxillary mucin solutions and their penetration into sheep nasal mucosa indicated greater diffusivity of modified chitosan nanoparticles compared to unmodified chitosan nanoparticles with the best results achieved for the chitosan grafted with poly(N-vinyl pyrrolidone). |
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| AbstractList | [Display omitted]
Transmucosal administration offers numerous advantages for drug delivery as it usually helps to avoid first pass metabolism, provides rapid onset of action, and is a non-invasive route. Mucosal surfaces are covered by a viscoelastic mucus gel layer which acts as a protective barrier preventing the entrance of harmful substances into the human tissues. This function of mucus also inhibits the diffusion of drugs and nano-formulations and can result in a significant reduction of their efficacy. The design of mucus-penetrating nanoparticles can overcome the barrier function of mucus which may lead to better therapeutic outcomes. In this study, chitosan was chemically modified by grafting short chains of poly(ethylene glycol), poly(2-hydroxyethyl acrylate), poly(2-ethyl-2-oxazoline), or poly(N-vinyl pyrrolidone) and the resulting chitosan derivatives were used to prepare nanoparticles using an ionic gelation method with sodium tripolyphosphate. These nanoparticles were characterised using dynamic light scattering, transmission electron microscopy, small-angle neutron scattering and nanoparticle tracking analysis. Small-angle neutron scattering data revealed the presence of a large amount of water inside these nanoparticles and lack of a heterogeneous internal structure. The nanogel model with low crosslinking density is suggested as the most feasible model to describe the structure of these nanoparticles. The studies of the behaviour of these nanoparticles in bovine submaxillary mucin solutions and their penetration into sheep nasal mucosa indicated greater diffusivity of modified chitosan nanoparticles compared to unmodified chitosan nanoparticles with the best results achieved for the chitosan grafted with poly(N-vinyl pyrrolidone). |
| Author | Lau, Wing Man Ways, Twana Mohammed M. Khutoryanskiy, Vitaliy V. Cegłowski, Michal Hoogenboom, Richard Filippov, Sergey K. Maji, Samarendra Glassner, Mathias King, Stephen |
| Author_xml | – sequence: 1 givenname: Twana Mohammed M. surname: Ways fullname: Ways, Twana Mohammed M. organization: Department of Pharmaceutics, College of Pharmacy, University of Sulaimani, Sulaimani, 46001 Kurdistan Region, Iraq – sequence: 2 givenname: Sergey K. surname: Filippov fullname: Filippov, Sergey K. organization: Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku 20520, Finland – sequence: 3 givenname: Samarendra surname: Maji fullname: Maji, Samarendra organization: Supramolecular Chemistry Group, Centre of Macromolecular Chemistry (CMaC), Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan, 281 S4, B-9000 Ghent, Belgium – sequence: 4 givenname: Mathias surname: Glassner fullname: Glassner, Mathias organization: Supramolecular Chemistry Group, Centre of Macromolecular Chemistry (CMaC), Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan, 281 S4, B-9000 Ghent, Belgium – sequence: 5 givenname: Michal surname: Cegłowski fullname: Cegłowski, Michal organization: Supramolecular Chemistry Group, Centre of Macromolecular Chemistry (CMaC), Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan, 281 S4, B-9000 Ghent, Belgium – sequence: 6 givenname: Richard surname: Hoogenboom fullname: Hoogenboom, Richard organization: Supramolecular Chemistry Group, Centre of Macromolecular Chemistry (CMaC), Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan, 281 S4, B-9000 Ghent, Belgium – sequence: 7 givenname: Stephen surname: King fullname: King, Stephen organization: ISIS Pulsed Neutron & Muon Source, Science and Technology Facilities Council, Rutherford Appleton Laboratory, Harwell Campus, Didcot OX11 0QX, UK – sequence: 8 givenname: Wing Man surname: Lau fullname: Lau, Wing Man organization: School of Pharmacy, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK – sequence: 9 givenname: Vitaliy V. surname: Khutoryanskiy fullname: Khutoryanskiy, Vitaliy V. email: v.khutoryanskiy@reading.ac.uk organization: Reading School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6AD, UK |
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| Keywords | Nanoparticles Drug delivery Chitosan Mucus penetration Diffusion |
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