Mucus-producing 3D cell culture models

Macedo, Maria Helena; Baião, Ana; Pinto, Soraia; Barros, Andreia S.; Almeida, Helena; Almeida, Andreia; Neves, José das

doi:10.1016/j.addr.2021.113993

Cited by 9 publications

(3 citation statements)

References 175 publications

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“…We have demonstrated potential interactions between human mucins and various drugs by relatively simple and rapid methods. The interaction of mucins with drugs has attracted much interest in the field of drug discovery research [ 6 , 7 , 23 , 25 ]. Going forward, it will be important to evaluate interactions with mucins in more detail for example using microscopy methods (TEM, AFM) and rheological studies, and there is a need to further develop evaluation systems that enable the rapid assessment of interactions.…”

Section: Discussionmentioning

confidence: 99%

Assessment of polymeric mucin–drug interactions

Kishimoto,

Ridley,

Inoue

et al. 2024

PLoS ONE

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Mucosal-delivered drugs have to pass through the mucus layer before absorption through the epithelial cell membrane. Although there has been increasing interest in polymeric mucins, a major structural component of mucus, potentially acting as important physiological regulators of mucosal drug absorption, there are no reports that have systematically evaluated the interaction between mucins and drugs. In this study, we assessed the potential interaction between human polymeric mucins (MUC2, MUC5B, and MUC5AC) and various drugs with different chemical profiles by simple centrifugal method and fluorescence analysis. We found that paclitaxel, rifampicin, and theophylline likely induce the aggregation of MUC5B and/or MUC2. In addition, we showed that the binding affinity of drugs for polymeric mucins varied, not only between individual drugs but also among mucin subtypes. Furthermore, we demonstrated that deletion of MUC5AC and MUC5B in A549 cells increased the cytotoxic effects of cyclosporin A and paclitaxel, likely due to loss of mucin-drug interaction. In conclusion, our results indicate the necessity to determine the binding of drugs to mucins and their potential impact on the mucin network property.

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Section: Discussionmentioning

confidence: 99%

Assessment of polymeric mucin–drug interactions

Kishimoto,

Ridley,

Inoue

et al. 2024

PLoS ONE

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“…With respect to mucus production, PAS staining and MUC2 immunostaining revealed the mucus layer in the partially laminated model. The thickness of the mucus layer can affect intestinal absorption [ 10 , 16 , 30 , 31 ]. Mucin proteins associate with lipids, which allows for hydrophobic interactions with drugs, decreasing diffusion rates in the mucus [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…Pharmaceutics 2023, 15, 2338 2 of 14 The mucus layer covering the gut epithelial surface functions as a barrier to certain drugs and delivery systems, as well as microorganisms and toxins [10]. Goblet cells are the second most abundant cells in the gastrointestinal epithelium that secrete mucus to cover the mucosal surface, acting as a physical barrier based on its viscosity and mesh structure [7].…”

Section: Introductionmentioning

confidence: 99%

Caco-2 Cell Sheet Partially Laminated with HT29-MTX Cells as a Novel In Vitro Model of Gut Epithelium Drug Permeability

Cheng,

Watanabe,

Ando

et al. 2023

Pharmaceutics

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The intestinal epithelial Caco-2 cell monolayer is a well-established in vitro model useful for predicting intestinal drug absorption in humans. Coculture models of Caco-2 and goblet-cell-like HT29-MTX cells have been developed to overcome the lack of a mucus layer; however, those models are much leakier compared to the intestinal epithelium. Here, we developed a partially laminated culture model where HT29-MTX cells were superimposed onto a Caco-2 monolayer to overcome this issue. A morphological study showed that the piled HT29-MTX cells were voluntarily incorporated into the Caco-2 monolayer, and mucus production was confirmed via periodic acid-Schiff and mucin protein 2 staining. Permeability was evaluated in terms of transepithelial electrical resistance (TEER) and the apparent permeability of paracellular markers with different molecular sizes. The partially laminated model maintained the high barrier function of the Caco-2 monolayer, whose permeability appeared adjustable according to the HT29-MTX/Caco-2 cell ratio. In contrast, the coculture models showed abnormally high permeability of those markers, correlated with low TEER. Thus, the partially laminated model enabled in vitro recapitulation of effective mucosal barrier function. Consequently, this novel model may be useful as an in vitro high-throughput evaluation system for enteral mucosal permeability and mucus-penetrating efficiency of drugs and nanocarriers.

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Tissue-based in vitro and ex vivo models for nasal permeability studies

Porfiryeva,

Sosnik

2024

Concepts and Models for Drug Permeability Studies

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Mucus-producing 3D cell culture models

Cited by 9 publications

References 175 publications

Assessment of polymeric mucin–drug interactions

Assessment of polymeric mucin–drug interactions

Caco-2 Cell Sheet Partially Laminated with HT29-MTX Cells as a Novel In Vitro Model of Gut Epithelium Drug Permeability

Tissue-based in vitro and ex vivo models for nasal permeability studies

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