Development and
            <i>In Vitro</i>
            Evaluation of Slippery Nanoparticles for Enhanced Diffusion Through Native Mucus

Laffleur, Flavia; Hintzen, Fabian; Shahnaz, Gul; Rahmat, Deni; Leithner, Katharina; Bernkop‐Schnürch, Andreas

doi:10.2217/nnm.13.26

Cited by 77 publications

(54 citation statements)

References 26 publications

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“…2). Since it has been reported that near-neutral potentials 14 and PEG modification could effectively reduce the interaction of 9 particles with mucus and enhance the particle stability, these results further demonstrated that the distinctive mucus-penetrating property resulted solely from the difference in shape.…”

mentioning

confidence: 65%

Rotation-Facilitated Rapid Transport of Nanorods in Mucosal Tissues

et al. 2016

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Mucus is a viscoelastic gel layer that typically protects exposed surfaces of the gastrointestinal (GI) tract, lung airways, and other mucosal tissues. Particles targeted to these tissues can be efficiently trapped and removed by mucus, thereby limiting the effectiveness of such drug delivery systems. In this study, we experimentally and theoretically demonstrated that cylindrical nanoparticles (NPs), such as mesoporous silica nanorods and calcium phosphate nanorods, have superior transport and trafficking capability in mucus compared with spheres of the same chemistry. The higher diffusivity of nanorods leads to deeper mucus penetration and a longer retention time in the GI tract than that of their spherical counterparts. Molecular simulations and stimulated emission of depletion (STED) microscopy revealed that this anomalous phenomenon can be attributed to the rotational dynamics of the NPs facilitated by the mucin fibers and the shear flow. These findings shed new light on the shape design of NP-based drug delivery systems targeted to mucosal and tumor sites that possess a fibrous structure/porous medium.

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mentioning

confidence: 65%

Rotation-Facilitated Rapid Transport of Nanorods in Mucosal Tissues

et al. 2016

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“…Positive charge caused adhesion to mucus fibers, while negative-charged NPs were repelled by the anionic barrier, and hydrophobic interactions can prevent permeation of uncharged particles (Aljayyoussi et al 2012). Transport data of polyacrylic acid/polyallylamine copolymers (neutral), polyacrylic acid (negative charge) and polyallylamine (positive charge) NPs through porcine mucus showed that neutral NPs can cross the mucus layer better than charged ones (Laffleur et al 2013).…”

Section: Mucus Layermentioning

confidence: 99%

Oral uptake of nanoparticles: human relevance and the role of in vitro systems

Frőhlich

Roblegg

2016

Arch Toxicol

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Nanoparticles (NPs) present in environment, consumer and health products, food and medical applications lead to a high degree of human exposure and concerns about potential adverse effects on human health. For the general population, the exposure through contact with the skin, inhalation and oral uptake are most relevant. Since in vivo testing is only partly able to study the effects of human oral exposure, physiologically relevant in vitro systems are being developed. This review compared the three routes taking into account the estimated concentration, size of the exposed area, morphology of the involved barrier and translocation rate. The high amounts of NPs in food, the large absorption area and the relatively high translocation rate identified oral uptake as most important portal of entry for NPs into the body. Changes of NP properties in the physiological fluids, mechanisms to cross mucus and epithelial barrier, and important issues in the use of laboratory animals for oral exposure are mentioned. The ability of in vitro models to address the varying conditions along the oro-gastrointestinal tract is discussed, and requirements for physiologically relevant in vitro testing of orally ingested NPs are listed.

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“…Furthermore, Laffleur et al could demonstrate with this system that 'slippery' neutral nanoparticles prepared via ionic interaction between the anionic polymer poly(acrylic) acid and the cationic polymer poly(allylamine) exhibited a high diffusion efficiency [30]. The neutral nanoparticles were compared with poly(allylamine) nanoparticles and poly(acrylic acid) nanoparticles prepared by ionic gelation with tripolyphosphate and calcium ions, respectively.…”

Section: Transwell-snapwell Systemmentioning

confidence: 99%