TY - JOUR
T1 - Mucus-penetrating nanoparticles based on chitosan grafted with various non-ionic polymers
T2 - Synthesis, structural characterisation and diffusion studies
AU - Ways, Twana Mohammed M.
AU - Filippov, Sergey K.
AU - Maji, Samarendra
AU - Glassner, Mathias
AU - Cegłowski, Michal
AU - Hoogenboom, Richard
AU - King, Stephen
AU - Lau, Wing Man
AU - Khutoryanskiy, Vitaliy V.
N1 - Funding Information:
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Twana Mohammed M. Ways reports financial support that was provided by HCED-Iraq and Ministry of Higher Education and Scientific Research-Kurdistan Regional Government. Vitaliy Khutoryanskiy reports financial support that was provided by the Leverhulme Trust.
Funding Information:
We are thankful to HCED-Iraq and Ministry of Higher Education and Scientific Research-Kurdistan Regional Government for their support. SKF and VVK are also grateful to the Leverhulme Trust for the visiting professorship grant (VP2-2020-013). Additionally, we are grateful to STFC for providing access to SANS beam time (proposal RB1810863). We acknowledge the assistance of staff at the Chemical Analysis Facility (CAF, University of Reading) in NMR, FTIR, fluorescence spectroscopy and TEM experiments.
Publisher Copyright:
© 2022 The Authors
PY - 2022/11/15
Y1 - 2022/11/15
N2 - 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).
AB - 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).
KW - Chitosan
KW - Diffusion
KW - Drug delivery
KW - Mucus penetration
KW - Nanoparticles
UR - http://www.scopus.com/inward/record.url?scp=85134573574&partnerID=8YFLogxK
U2 - 10.1016/j.jcis.2022.06.126
DO - 10.1016/j.jcis.2022.06.126
M3 - Article
C2 - 35797869
AN - SCOPUS:85134573574
SN - 0021-9797
VL - 626
SP - 251
EP - 264
JO - Journal of Colloid and Interface Science
JF - Journal of Colloid and Interface Science
ER -