Mucus as a barrier to lipophilic drugs

Sigurđsson, Hákon Hrafn; Kirch, Julian; Lehr, Claus‐Michael

doi:10.1016/j.ijpharm.2013.05.040

Cited by 225 publications

(186 citation statements)

References 114 publications

Supporting

Mentioning

181

Contrasting

Order By: Relevance

“…Mucus layers are present and important for intestinal and lung barriers including drug absorption [43]. In a recent three-dimensional model mimicking the microenvironment of the small intestine transport properties closer to the in vivo situation were measured [44].…”

Section: General Considerations and Comparison With Other Biochips Momentioning

confidence: 99%

A versatile lab-on-a-chip tool for modeling biological barriers

Walter

Valkai

Kincses

et al. 2016

Sensors and Actuators B: Chemical

141

156

View full text Add to dashboard Cite

Keywords: Microfluidics Lung and intestinal epithelial cells Endothelial cells Blood-brain barrier PermeabilityTrans-epithelial/endothelial electric resistance a b s t r a c t Models of biological barriers are important to study physiological functions, transport mechanisms, drug delivery and pathologies. However, there are only a few integrated biochips which are able to monitor several of the crucial parameters of cell-culture-based barrier models. The aim of this study was to design and manufacture a simple but versatile device, which allows a complex investigation of barrier functions. The following functions and measurements are enabled simultaneously: co-culture of 2 or 3 types of cells; flow of culture medium; visualization of the entire cell layer by microscopy; real-time transcellular electrical resistance monitoring; permeability measurements. To this end, a poly(dimethylsiloxane)-based biochip with integrated transparent gold electrodes and with a possibility to connect to a peristaltic pump was built. Unlike previous systems, the structure of the device allowed a constant visual observation of cell growth over the whole membrane surface. Morphological characterization of the layers was also accomplished by immunohistochemical staining. The chip was applied to monitor and characterize models of the intestinal and lung epithelial barriers, and the blood-brain barrier. The models were established using human Caco-2 intestinal and A549 lung epithelial cell lines, hCMEC/D3 human brain endothelial cell line and primary rat brain endothelial cells co-cultured with primary astrocytes and brain pericytes. This triple primary co-culture blood-brain barrier model was assembled on a lab-on-a-chip device and investigated under fluid flow for the first time. Such a versatile tool is expected to facilitate the kinetic investigation of various biological barriers.

show abstract

Section: General Considerations and Comparison With Other Biochips Momentioning

confidence: 99%

A versatile lab-on-a-chip tool for modeling biological barriers

Walter

Valkai

Kincses

et al. 2016

Sensors and Actuators B: Chemical

141

156

View full text Add to dashboard Cite

show abstract

“…To overcome this biological barrier caused by some novel inhalation pharmaceuticals, functionalized and nontoxic nanocarriers can be used. Inspired from viruses, nanosized particles with neutrally charged coatings such as polyethylene glycol (PEG) can efficiently penetrate the mucus layer in contrast to charged particles (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

A Model for the Transient Subdiffusive Behavior of Particles in Mucus

Ernst¹,

John

Guenther³

et al. 2017

Biophysical Journal

Self Cite

View full text Add to dashboard Cite

In this study we have applied a model to explain the reported subdiffusion of particles in mucus, based on the measured mean squared displacements (MSD). The model considers Brownian diffusion of particles in a confined geometry, made from permeable membranes. The applied model predicts a normal diffusive behavior at very short and long time lags, as observed in several experiments. In between these timescales, we find that the ''subdiffusive'' regime is only a transient effect, MSDft a ; a < 1. The only parameters in the model are the diffusion-coefficients at the limits of very short and long times, and the distance between the permeable membranes L. Our numerical results are in agreement with published experimental data for realistic assumptions of these parameters. Finally, we show that only particles with a diameter less than 40 nm are able to pass through a mucus layer by passive Brownian motion.

show abstract

“…Mucoadhesion, which refers to attachment to mucus either by hydrogen bonding or electrostatic binding with mucin layer, may influence drug absorption (Sigurdsson et al 2013). The most common mucoadhesives employed in ocular formulations are water-soluble polymers that cannot cross ocular barriers such as the polyacrylic derivatives including carbomers and thiomers, xanthan gum, carrageenan, chitosan, and hyaluronic acid.…”

Section: Mucoadhesive Formulationsmentioning

confidence: 99%