Generating an In Vitro Gut Model with Physiologically Relevant Biophysical Mucus Properties

McCright, Jacob; Sinha, Arnav; Maisel, Katharina

doi:10.1007/s12195-022-00740-0

Cited by 9 publications

(17 citation statements)

References 57 publications

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“…75,79 The epithelial permeability and biophysical properties of mucus in Caco-2/HT29-MTX co-culture cells have been shown to be physiologically relevant, with the mucus layer exhibiting properties similar to that of existing animal models. 81 Intestinal epithelial cells can also be grown into a 3D, spheroid conformation to represent the morphological geometry of the gut. Several groups have developed 3D Caco-2 spheroids by seeding Caco-2 cells in ultralow attachment tissue culture materials.…”

Section: Experimental Models To Study Nanoparticles' Transport Mechan...mentioning

confidence: 99%

“…Our lab has recently generated a physiologically relevant in vitro transwell gut model using Caco-2 and HT29MTX cell co-culture, and we have shown the permeability of nanoparticles across the basolateral side of the gut model. 81 Several other studies have also reported the transcytosis of nanoparticles across the intestinal epithelium, though our understanding of exocytosis is still much less than that of endocytosis. Thus, further research is needed to shed light on the exocytosis mechanisms of nanoparticle transport across GI epithelial cells.…”

Section: Exocytosismentioning

confidence: 99%

“…However, the lack of mucus production by Caco-2 monolayers and the higher expression of tight junction proteins, and lower expression of many drug-metabolizing enzymes, limits the applicability of this monolayer model. , To include mucus, Caco-2 cells can also be co-cultured with goblet-like cells, such as HT29-MTX cells. HT29-MTX cells are a human colon adenocarcinoma cell line that has been treated with methotrexate (MTX) to induce differentiation into goblet-like cells. , When combined, Caco-2/HT29-MTX co-culture monolayer models mimic the mucus-coated intestinal epithelium and can provide information on the transport, absorption, and penetration properties of nanoparticles in the mucus gel of intestinal environments. , The epithelial permeability and biophysical properties of mucus in Caco-2/HT29-MTX co-culture cells have been shown to be physiologically relevant, with the mucus layer exhibiting properties similar to that of existing animal models …”

Section: Experimental Models To Study Nanoparticles’ Transport Mechan...mentioning

confidence: 99%

“…The process of exocytosis is complex and depends on various factors that lead to the concept of “easy to enter, hard to exit” transcytosis. Our lab has recently generated a physiologically relevant in vitro transwell gut model using Caco-2 and HT29MTX cell co-culture, and we have shown the permeability of nanoparticles across the basolateral side of the gut model . Several other studies have also reported the transcytosis of nanoparticles across the intestinal epithelium, though our understanding of exocytosis is still much less than that of endocytosis.…”

Section: Exocytosismentioning

confidence: 99%

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Mechanisms of Nanoparticle Transport across Intestinal Tissue: An Oral Delivery Perspective

2023

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Oral drug administration has been a popular choice due to patient compliance and limited clinical resources. Orally delivered drugs must circumvent the harsh gastrointestinal (GI) environment to effectively enter the systemic circulation.The GI tract has a number of structural and physiological barriers that limit drug bioavailability including mucus, the tightly regulated epithelial layer, immune cells, and associated vasculature. Nanoparticles have been used to enhance oral bioavailability of drugs, as they can act as a shield to the harsh GI environment and prevent early degradation while also increasing uptake and transport of drugs across the intestinal epithelium. Evidence suggests that different nanoparticle formulations may be transported via different intracellular mechanisms to cross the intestinal epithelium. Despite the existence of a significant body of work on intestinal transport of nanoparticles, many key questions remain: What causes the poor bioavailability of the oral drugs? What factors contribute to the ability of a nanoparticle to cross different intestinal barriers? Do nanoparticle properties such as size and charge influence the type of endocytic pathways taken? In this Review, we summarize the different components of intestinal barriers and the types of nanoparticles developed for oral delivery. In particular, we focus on the various intracellular pathways used in nanoparticle internalization and nanoparticle or cargo translocation across the epithelium. Understanding the gut barrier, nanoparticle characteristics, and transport pathways may lead to the development of more therapeutically useful nanoparticles as drug carriers.

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Section: Experimental Models To Study Nanoparticles' Transport Mechan...mentioning

confidence: 99%

Section: Exocytosismentioning

confidence: 99%

Section: Experimental Models To Study Nanoparticles’ Transport Mechan...mentioning

confidence: 99%

Section: Exocytosismentioning

confidence: 99%

See 2 more Smart Citations

Mechanisms of Nanoparticle Transport across Intestinal Tissue: An Oral Delivery Perspective

2023

Self Cite

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“…In a cocultured in vitro model (HT29‐MTX and Caco2 cells), the thickness of the derived mucus depended on the ratio of the HT29‐MTX and Caco2 cells. [ 57 ] For example, when cultured alone for 21 days, HT29‐MTX cells produced a mucus layer with a thickness of 175±37 µm. However, when cocultured with Caco2 cells, the height of the derived mucus layer decreased.…”

Section: Current Methods Of Obtaining Mammalian Free‐flowing Mucus An...mentioning

confidence: 99%

Mucosa‐Mimetic Materials for the Study of Intestinal Homeostasis and Disease

Donahue

Sahoo

Rudolph

et al. 2023

Adv Healthcare Materials

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Mucus is a viscoelastic hydrogel that lines and protects the epithelial surfaces of the body that houses commensal microbiota and functions in host defense against pathogen invasion. As a first‐line physical and biochemical barrier, intestinal mucus is involved in immune surveillance and spatial organization of the microbiome, while dysfunction of the gut mucus barrier is implicated in several diseases. Mucus can be collected from a variety of mammalian sources for study, however, established methods are challenging in terms of scale and efficiency, as well as with regard to rheological similarity to native human mucus. Therefore, there is a need for mucus‐mimetic hydrogels that more accurately reflect the physical and chemical profile of the in vivo human epithelial environment to enable the investigation of the role of mucus in human disease and interactions with the intestinal microbiome. This review will evaluate the material properties of synthetic mucus mimics to date designed to address the above need, with a focus toward an improved understanding of the biochemical and immunological functions of these biopolymers related to utility for research and therapeutic applications.

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Cellular interplay to 3D in vitro microphysiological disease model: cell patterning microbiota–gut–brain axis

Alam,

Nair,

Mukherjee

et al. 2024

Bio-des. Manuf.

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Generating an In Vitro Gut Model with Physiologically Relevant Biophysical Mucus Properties

Cited by 9 publications

References 57 publications

Mechanisms of Nanoparticle Transport across Intestinal Tissue: An Oral Delivery Perspective

Mechanisms of Nanoparticle Transport across Intestinal Tissue: An Oral Delivery Perspective

Mucosa‐Mimetic Materials for the Study of Intestinal Homeostasis and Disease

Cellular interplay to 3D in vitro microphysiological disease model: cell patterning microbiota–gut–brain axis

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