A novel microfluidic mucus-chip for studying the permeation of compounds over the mucus barrier

Elberskirch, Linda; Knoll, Thorsten; Moosmann, Aline; Wilhelm, Nadine; Briesen, Hagen von; Wagner, Sylvia

doi:10.1016/j.jddst.2019.101248

Cited by 18 publications

(21 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since the velocity slip induced by the entrapped gas pockets on an SH-textured surface reduces the pressure drop, such surfaces alleviate the pumping power requirement in microfluidic devices (Davis and Lauga 2009). However, most of the microfluidic devices operate with non-Newtonian liquids, such as blood (Laxmi et al 2020), mucus (Elberskirch et al 2019), polymeric liquids (Raoufi et al 2019) and even colloidal suspensions (Liu et al 2020). Despite the importance of such non-Newtonian liquids in microfluidics, the hydrodynamic drag reduction of these liquids is rarely investigated in the context of pressure-driven flow through SH-textured micro-channels.…”

Section: Introductionmentioning

confidence: 99%

Hydrodynamic drag reduction of shear-thinning liquids in superhydrophobic textured microchannels

Gaddam

Sharma

Ahuja

et al. 2021

Microfluid Nanofluid

View full text Add to dashboard Cite

Super-hydrophobic textured surfaces reduce hydrodynamic drag in pressure-driven laminar flows in micro-channels. However, despite the wide usage of non-Newtonian liquids in microfluidic devices, the flow behaviour of such liquids was rarely examined so far in the context of friction reduction in textured super-hydrophobic micro-channels. Thus, we have investigated the influence of topologically different rough surfaces on friction reduction of shear-thinning liquids in micro-channels. First, the friction factor ratio (a ratio of friction factor on a textured surface to a plain surface) on generic surface textures, such as posts, holes, longitudinal and transverse ribs, was estimated numerically over a range of Carreau number as a function of microchannel constriction ratio, gas fraction and power-law exponent. Resembling the flow behaviour of Newtonian liquids, the longitudinal ribs and posts have exhibited significantly less flow friction than the transverse ribs and holes while the friction factor ratios of all textures has exhibited non-monotonic variation with the Carreau number. While the minima of the friction factor ratio were noticed at a constant Carreau number irrespective of the microchannel constriction ratio, the minima have shifted to a higher Carreau number with an increase in the power-law index and gas fraction. Experiments were also conducted with aqueous Xanthan Gum liquids in micro-channels. The flow enhancement (the flow rate with super-hydrophobic textures with respect to a smooth surface) exhibited a non-monotonic behaviour and attenuated with an increase in power-law index tantamount to simulations. The results will serve as a guide to design frictionless micro-channels when employing non-Newtonian liquids.

show abstract

Section: Introductionmentioning

confidence: 99%

Hydrodynamic drag reduction of shear-thinning liquids in superhydrophobic textured microchannels

Gaddam

Sharma

Ahuja

et al. 2021

Microfluid Nanofluid

View full text Add to dashboard Cite

show abstract

“…In the past decades, several different techniques have been established to study the interplay between drugs/formulations and the mucus layer, such as diffusion studies [6,7], microscopy-based techniques [8], SANS (small-angle neutron scattering) [9], NMR (nuclear magnetic resonance) methodology [10], together with in vivo [8] and in vitro models [11].…”

Section: Introductionmentioning

confidence: 99%

Impact of Mucin on Drug Diffusion: Development of a Straightforward In Vitro Method for the Determination of Drug Diffusivity in the Presence of Mucin

et al. 2020

View full text Add to dashboard Cite

Mucosal drug delivery accounts for various administration routes (i.e., oral, vaginal, ocular, pulmonary, etc.) and offers a vast surface for the permeation of drugs. However, the mucus layer which shields and lubricates all mucosal tissues can compromise drugs from reaching the epithelial site, thus affecting their absorption and therapeutic effect. Therefore, the effect of the mucus layer on drug absorption has to be evaluated early in the drug-development phase, prior to in vivo studies. For this reason, we developed a simple, cost-effective and reproducible method employing UV-visible localized spectroscopy for the assessment of the interaction between mucin and drugs with different physicochemical characteristics. The mucin–drug interaction was investigated by measuring the drug relative diffusivity (Drel) in the presence of mucin, and the method was validated by fitting experimental and mathematical data. In vitro permeability studies were also performed using the mucus-covered artificial permeation barrier (mucus–PVPA, Phospholipid Vesicle-based Permeation Assay) for comparison. The obtained results showed that the diffusion of drugs was hampered by the presence of mucin, especially at higher concentrations. This novel method proved to be suitable for the investigation on the extent of mucin–drug interaction and can be successfully used to assess the impact that the mucus layer has on drug absorption.

show abstract

“…After the static and fluidic permeation studies, the model substances in the apical and basolateral CCM were quantified via HPLC measurements as described in Elberskirch et al [52]. The amounts of caffeine and diclofenac were determined by an Agilent 1260 HPLC (Agilent Technologies, Santa Clara, CA, USA).…”

Section: High-performance Liquid Chromatography (Hplc) Analysismentioning

confidence: 99%

“…HPLC gradient conditions according to Elberskirch et al[52]. Solvent A: water; solvent B: acetonitrile; solvent C: 0.1% trifluoroacetic acid in water.…”

mentioning

confidence: 99%

In Vitro–In Silico Modeling of Caffeine and Diclofenac Permeation in Static and Fluidic Systems with a 16HBE Lung Cell Barrier

et al. 2022

View full text Add to dashboard Cite

Static in vitro permeation experiments are commonly used to gain insights into the permeation properties of drug substances but exhibit limitations due to missing physiologic cell stimuli. Thus, fluidic systems integrating stimuli, such as physicochemical fluxes, have been developed. However, as fluidic in vitro studies display higher complexity compared to static systems, analysis of experimental readouts is challenging. Here, the integration of in silico tools holds the potential to evaluate fluidic experiments and to investigate specific simulation scenarios. This study aimed to develop in silico models that describe and predict the permeation and disposition of two model substances in a static and fluidic in vitro system. For this, in vitro permeation studies with a 16HBE cellular barrier under both static and fluidic conditions were performed over 72 h. In silico models were implemented and employed to describe and predict concentration–time profiles of caffeine and diclofenac in various experimental setups. For both substances, in silico modeling identified reduced apparent permeabilities in the fluidic compared to the static cellular setting. The developed in vitro–in silico modeling framework can be expanded further, integrating additional cell tissues in the fluidic system, and can be employed in future studies to model pharmacokinetic and pharmacodynamic drug behavior.

show abstract

A novel microfluidic mucus-chip for studying the permeation of compounds over the mucus barrier

Cited by 18 publications

References 24 publications

Hydrodynamic drag reduction of shear-thinning liquids in superhydrophobic textured microchannels

Hydrodynamic drag reduction of shear-thinning liquids in superhydrophobic textured microchannels

Impact of Mucin on Drug Diffusion: Development of a Straightforward In Vitro Method for the Determination of Drug Diffusivity in the Presence of Mucin

In Vitro–In Silico Modeling of Caffeine and Diclofenac Permeation in Static and Fluidic Systems with a 16HBE Lung Cell Barrier

Contact Info

Product

Resources

About