A bespoke microfluidic pharmacokinetic compartment model for drug absorption using artificial cell membranes

Korner, Jaime L.; Stephenson, Elanna B.; Elvira, Katherine S.

doi:10.1039/d0lc00263a

Cited by 16 publications

(33 citation statements)

References 59 publications

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“…DIBs present another advantage as they form asymmetric membranes in a simple yet controllable manner by dispersing different lipid mixtures in each droplet [ 138 , 139 ]. Furthermore, these emulsion systems allow for the assembly of membranous networks for investigating synthetic tissues [ 140 ] and bespoke model environment for studying transmembrane exchanges [ 141 ].…”

Section: Model Membranes: Manufactures and Resulting Propertiesmentioning

confidence: 99%

Characterizing the Structure and Interactions of Model Lipid Membranes Using Electrophysiology

El-Beyrouthy

Freeman

2021

Membranes

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The cell membrane is a protective barrier whose configuration determines the exchange both between intracellular and extracellular regions and within the cell itself. Consequently, characterizing membrane properties and interactions is essential for advancements in topics such as limiting nanoparticle cytotoxicity. Characterization is often accomplished by recreating model membranes that approximate the structure of cellular membranes in a controlled environment, formed using self-assembly principles. The selected method for membrane creation influences the properties of the membrane assembly, including their response to electric fields used for characterizing transmembrane exchanges. When these self-assembled model membranes are combined with electrophysiology, it is possible to exploit their non-physiological mechanics to enable additional measurements of membrane interactions and phenomena. This review describes several common model membranes including liposomes, pore-spanning membranes, solid supported membranes, and emulsion-based membranes, emphasizing their varying structure due to the selected mode of production. Next, electrophysiology techniques that exploit these structures are discussed, including conductance measurements, electrowetting and electrocompression analysis, and electroimpedance spectroscopy. The focus of this review is linking each membrane assembly technique to the properties of the resulting membrane, discussing how these properties enable alternative electrophysiological approaches to measuring membrane characteristics and interactions.

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Section: Model Membranes: Manufactures and Resulting Propertiesmentioning

confidence: 99%

Characterizing the Structure and Interactions of Model Lipid Membranes Using Electrophysiology

El-Beyrouthy

Freeman

2021

Membranes

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“…Recently, this approach was revisited to enable the formation of a line of three droplets, with different aqueous environments representing the intestinal lumen, the enterocyte cytoplasm, and the blood lumen ( Figure 12 ). Transport kinetics of fluorescein from intestine to enterocyte to blood droplet compartments could be monitored directly in the microfluidic device using fluorescence microscopy [ 137 ].…”

Section: On-chip Analysis Of Food Dropletsmentioning

confidence: 99%

“…Reprinted from [ 134 ] with permission from Elsevier. Bottom: Microfluidic device for the analysis of bioactive compound transport kinetics between aqueous droplets, as designed in [ 137 ]. Image courtesy of Katherine Elvira, University of Victoria, Canada.…”

Section: Figurementioning

confidence: 99%

Droplet Microfluidics for Food and Nutrition Applications

et al. 2021

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Droplet microfluidics revolutionizes the way experiments and analyses are conducted in many fields of science, based on decades of basic research. Applied sciences are also impacted, opening new perspectives on how we look at complex matter. In particular, food and nutritional sciences still have many research questions unsolved, and conventional laboratory methods are not always suitable to answer them. In this review, we present how microfluidics have been used in these fields to produce and investigate various droplet-based systems, namely simple and double emulsions, microgels, microparticles, and microcapsules with food-grade compositions. We show that droplet microfluidic devices enable unprecedented control over their production and properties, and can be integrated in lab-on-chip platforms for in situ and time-resolved analyses. This approach is illustrated for on-chip measurements of droplet interfacial properties, droplet–droplet coalescence, phase behavior of biopolymer mixtures, and reaction kinetics related to food digestion and nutrient absorption. As a perspective, we present promising developments in the adjacent fields of biochemistry and microbiology, as well as advanced microfluidics–analytical instrument coupling, all of which could be applied to solve research questions at the interface of food and nutritional sciences.

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“…The integration of these types of technologies into the discovery process is more straightforward since they provide information that can then be verified using mechanisms that are approved as part of The top-left image shows the artificial cells that can be used to form a new type of in vitro pharmacokinetic compartment model using droplets to determine drug behavior early in the discovery process. Reproduced from [53], with permission from the Royal Society of Chemistry. The top-right image shows the design of the microfluidic device for combinatorial drug screening on patient-derived samples using droplets.…”

Section: Microfluidic Technologies For Personalized Medicinementioning

confidence: 99%

“…The hypothesis is that biomimetic tests that can be used early in the discovery process would help to select lead candidates with a greater degree of confidence regarding their future in vivo behavior. We have developed a microfluidic device to build bespoke artificial cells from the bottom up for use as a new type of pharmacokinetic compartment model for intestinal epithelial permeability [53] (Figure 1). In this work, we used a droplet-based PDMS device to model the path that a drug proxy takes from the intestine into an enterocyte (cells that line the intestine) and then into the bloodstream.…”

Section: Microfluidic Platforms For the Creation Of Artificial Cells And Tissuesmentioning

confidence: 99%

Microfluidic technologies for drug discovery and development: friend or foe?

Elvira

2021

Trends in Pharmacological Sciences

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A bespoke microfluidic pharmacokinetic compartment model for drug absorption using artificial cell membranes

Abstract: A new type of pharmacokinetic compartment model using artificial cell membranes that predicts intestinal absorption three times more accurately than the current state of the art.

Cited by 16 publications

References 59 publications

Characterizing the Structure and Interactions of Model Lipid Membranes Using Electrophysiology

Characterizing the Structure and Interactions of Model Lipid Membranes Using Electrophysiology

Droplet Microfluidics for Food and Nutrition Applications

Microfluidic technologies for drug discovery and development: friend or foe?

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