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

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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.
Keywords
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

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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.
@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},
}

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