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Mucus-penetrating solid lipid nanoparticles for the treatment of cystic fibrosis : proof of concept, challenges and pitfalls

N Nafee, Katrien Forier UGent, Kevin Braeckmans UGent and M Schneider (2018) EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS. 124. p.125-137
abstract
Nanocarrier-mediated transmucosal drug delivery based on conventional mucoadhesive, muco-inert or mucus penetrating nanoparticles (NPs) is a growing field especially in challenging diseases like cystic fibrosis (CF). Efficacy of such systems dictates profound investigation of particle-mucus interaction and factors governing the whole process. Although variable techniques studying particle diffusion in mucus have been introduced, standardized procedures are lacking. The study comprised different methods based on micro- and macro-displacement as well as colloidal stability and turbidimetric experiments. Artificial sputum medium (ASM), CF sputum and mucus-secreting cell line (Calu-3 air interface culture, AIC) were applied. Solid lipid nanoparticles (SLNs) coated with variable hydrophilic sheath (poloxamer, Tween 80 or PVA) represented the nanocarriers under investigation. Both micro-displacement studies based on single particle tracking and macro-displacement experiments based on 3D-time laps confocal imaging revealed faster diffusion of poloxamer- > Tween- > PVAcoated SLNs. Compared to ASM, CF sputum showed not only lower diffusion rates but also remarkable discrepancies in particle-mucus diffusion rate due to sputum heterogenicity. Meanwhile, in case of Calu-3 AIC, thickness of the mucosal layer as well as density of mucus network were key determinants in the diffusion process. The points emphasized in this study highlight the road towards in vivo relevant particle-mucus interaction research.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
Nanocarriers, Mucus, Particle-mucus interaction, Confocal 3D-time laps imaging, Multiple particle tracking, SINGLE-PARTICLE TRACKING, MUCOADHESIVE NANOPARTICLES, DRUG-DELIVERY, BIODEGRADABLE NANOPARTICLES, CARRIER SYSTEMS, BARRIER, INFECTIONS, TRANSPORT, DYNAMICS, OVERCOME
journal title
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Eur. J. Pharm. Biopharm.
volume
124
pages
125 - 137
Web of Science type
Article
Web of Science id
000425839500014
ISSN
0939-6411
DOI
10.1016/j.ejpb.2017.12.017
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
8545068
handle
http://hdl.handle.net/1854/LU-8545068
date created
2018-01-16 10:24:11
date last changed
2018-04-26 08:54:29
@article{8545068,
  abstract     = {Nanocarrier-mediated transmucosal drug delivery based on conventional mucoadhesive, muco-inert or mucus penetrating nanoparticles (NPs) is a growing field especially in challenging diseases like cystic fibrosis (CF). Efficacy of such systems dictates profound investigation of particle-mucus interaction and factors governing the whole process. Although variable techniques studying particle diffusion in mucus have been introduced, standardized procedures are lacking. The study comprised different methods based on micro- and macro-displacement as well as colloidal stability and turbidimetric experiments. Artificial sputum medium (ASM), CF sputum and mucus-secreting cell line (Calu-3 air interface culture, AIC) were applied. Solid lipid nanoparticles (SLNs) coated with variable hydrophilic sheath (poloxamer, Tween 80 or PVA) represented the nanocarriers under investigation. Both micro-displacement studies based on single particle tracking and macro-displacement experiments based on 3D-time laps confocal imaging revealed faster diffusion of poloxamer- {\textrangle} Tween- {\textrangle} PVAcoated SLNs. Compared to ASM, CF sputum showed not only lower diffusion rates but also remarkable discrepancies in particle-mucus diffusion rate due to sputum heterogenicity. Meanwhile, in case of Calu-3 AIC, thickness of the mucosal layer as well as density of mucus network were key determinants in the diffusion process. The points emphasized in this study highlight the road towards in vivo relevant particle-mucus interaction research.},
  author       = {Nafee, N and Forier, Katrien and Braeckmans, Kevin and Schneider, M},
  issn         = {0939-6411},
  journal      = {EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS},
  keyword      = {Nanocarriers,Mucus,Particle-mucus interaction,Confocal 3D-time laps imaging,Multiple particle tracking,SINGLE-PARTICLE TRACKING,MUCOADHESIVE NANOPARTICLES,DRUG-DELIVERY,BIODEGRADABLE NANOPARTICLES,CARRIER SYSTEMS,BARRIER,INFECTIONS,TRANSPORT,DYNAMICS,OVERCOME},
  language     = {eng},
  pages        = {125--137},
  title        = {Mucus-penetrating solid lipid nanoparticles for the treatment of cystic fibrosis : proof of concept, challenges and pitfalls},
  url          = {http://dx.doi.org/10.1016/j.ejpb.2017.12.017},
  volume       = {124},
  year         = {2018},
}

Chicago
Nafee, N, Katrien Forier, Kevin Braeckmans, and M Schneider. 2018. “Mucus-penetrating Solid Lipid Nanoparticles for the Treatment of Cystic Fibrosis : Proof of Concept, Challenges and Pitfalls.” European Journal of Pharmaceutics and Biopharmaceutics 124: 125–137.
APA
Nafee, N., Forier, K., Braeckmans, K., & Schneider, M. (2018). Mucus-penetrating solid lipid nanoparticles for the treatment of cystic fibrosis : proof of concept, challenges and pitfalls. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 124, 125–137.
Vancouver
1.
Nafee N, Forier K, Braeckmans K, Schneider M. Mucus-penetrating solid lipid nanoparticles for the treatment of cystic fibrosis : proof of concept, challenges and pitfalls. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS. 2018;124:125–37.
MLA
Nafee, N, Katrien Forier, Kevin Braeckmans, et al. “Mucus-penetrating Solid Lipid Nanoparticles for the Treatment of Cystic Fibrosis : Proof of Concept, Challenges and Pitfalls.” EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS 124 (2018): 125–137. Print.