Mucus thickness in the gastrointestinal tract of laboratory animals

Varum, Felipe; Veiga, Francisco; Sousa, João; Basit, Abdul W.

doi:10.1111/j.2042-7158.2011.01399.x

Cited by 61 publications

(48 citation statements)

References 68 publications

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“…Measurements of mucus thickness in cryostat sections of various laboratory animal species (rat, rabbit, pig) identified a greater thickness in the fundus region of the stomach in the pig (191-222 µm) than in the rabbit (155-277 µm) and in the rat (31-69 µm) (Varum et al 2012). Along the small intestine, mucus was thicker in the rabbit (73-148 µm), followed by the pig (25-54 µm) and the rat (31-34 µm).…”

Section: Oral Routementioning

confidence: 99%

Oral uptake of nanoparticles: human relevance and the role of in vitro systems

Frőhlich

Roblegg

2016

Arch Toxicol

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Nanoparticles (NPs) present in environment, consumer and health products, food and medical applications lead to a high degree of human exposure and concerns about potential adverse effects on human health. For the general population, the exposure through contact with the skin, inhalation and oral uptake are most relevant. Since in vivo testing is only partly able to study the effects of human oral exposure, physiologically relevant in vitro systems are being developed. This review compared the three routes taking into account the estimated concentration, size of the exposed area, morphology of the involved barrier and translocation rate. The high amounts of NPs in food, the large absorption area and the relatively high translocation rate identified oral uptake as most important portal of entry for NPs into the body. Changes of NP properties in the physiological fluids, mechanisms to cross mucus and epithelial barrier, and important issues in the use of laboratory animals for oral exposure are mentioned. The ability of in vitro models to address the varying conditions along the oro-gastrointestinal tract is discussed, and requirements for physiologically relevant in vitro testing of orally ingested NPs are listed.

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Section: Oral Routementioning

confidence: 99%

Oral uptake of nanoparticles: human relevance and the role of in vitro systems

Frőhlich

Roblegg

2016

Arch Toxicol

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“…Mucus is often referred to as a single layer, but it is important to emphasize that studies have identified two layers, namely (i) a firmly adherent mucus layer in connection with the glycocalyx of the epithelial cells and (ii) an overlying loosely adherent layer of mucus [24,25]. As there is discrepancy as to whether the mucus in the small intestine is composed of one or two layers [7,24], the practice of referring to mucus as a single layer is followed in this paper unless stated otherwise.…”

Section: Mucus Function and Compositionmentioning

confidence: 99%

“…In the rat, the total mucus thickness in the gastrointestinal tract was found to range from 120 to 830 lm [24]. Generally, the thickness has been found to be greater in the stomach than in the large intestine, and the small intestine is the gastrointestinal segment with the thinnest mucus lining [24][25][26]. The thickness of the adherent mucus layer is, in contrast to the thickness of the loosely adherent layer, assumed to be independent of hydration and luminal activity [9].…”

Section: Mucus Function and Compositionmentioning

confidence: 99%

“…The thickness of the adherent mucus layer is, in contrast to the thickness of the loosely adherent layer, assumed to be independent of hydration and luminal activity [9]. One study comparing the mucus thicknesses in the rat, rabbit and pig found that the mucus distribution in the pig resembled the human the most [25]. However, in that study, the thickness of the adherent mucus layer was found to be rather uniform throughout the rat gastrointestinal tract (in the range of 30-60 lm), which is in contrast to a previous determination of the adherent mucus layer ranging from 15 to 120 lm in thickness within the rat gastrointestinal tract [24].…”

Section: Mucus Function and Compositionmentioning

confidence: 99%

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Mucus as a Barrier to Drug Delivery – Understanding and Mimicking the Barrier Properties

Boegh

Nielsen

2014

Basic Clin Pharma Tox

264

185

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Viscoelastic mucus lines all mucosal surfaces of the body and forms a potential barrier to mucosal drug delivery. Mucus is mainly composed of water and mucins; high molecular weight glycoproteins forming an entangled network. Consequently, mucus forms a steric barrier, and due to its negative charge and hydrophobic domains, the overall hydrophilic mucus also presents an interactive barrier limiting the free diffusion of components within and through the mucus. Furthermore, mucus is a dynamic barrier due to its continuous secretion and shedding from the mucosal surfaces. Mucus is thus a highly complex gel barrier to drug delivery. Current knowledge of mucus characteristics and barrier properties, as achieved by state-of-the-art methodologies, is the topic of this MiniReview emphasizing the gastrointestinal mucus and an overall focus on oral drug delivery. Cell culture-based in vitro models are well-established as essential tools in drug research and development, but traditionally, mucus-containing models have only rarely been applied. However, a number of mucus-containing in vitro models have recently been described in the literature, and their properties and applications will be reviewed and discussed. Finally, studies of peptide and protein drug diffusion in and through mucus and studies of mucus-penetrating nanoparticles are included to illustrate the mucus as a potentially important barrier to obtain sufficient bioavailability of orally administered drugs, and thus an important parameter to address in the development of future oral drug delivery systems.

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“…Since pigs also have an omnivorous diet, their GI tract is very much comparable to that of humans [6,[28][29][30][31]. Since porcine tissue is generally more easily available than healthy human intestinal tissue it allows a more systematic approach to investigate (regional) intestinal absorption of NPs from a biorelevant matrix.…”

Section: Introductionmentioning

confidence: 99%

Prediction of Oral Absorption of Nanoparticles from Biorelevant Matrices Using a Combination of Physiologically Relevant In Vitro and Ex Vivo Models

Westerhout¹,

Bellmann²,

Ee³

et al. 2017

J Food Chem Nanotechol

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The application of nanoparticles (NPs) in food products is ever increasing. For consumer safety it is essential to know the human oral bioavailability of these NPs. In the present study, a combination of physiologically relevant in vitro and ex vivo models are presented, which combined are considered to predict human intestinal digestion and absorption of NPs more accurately than commonly applied animal or cellular studies.First, a computer controlled dynamic in vitro gastrointestinal model (tiny-TIM) is used for simulation of the digestive processes upon gastro-intestinal passage of non-biodegradable aminated, carboxylated, or unmodified fluorescent polystyrene NPs (PS-NPs). Then, the pretreated (digested) PS-NPs were consequently evaluated for absorption using ex vivo porcine intestinal tissue.In this study, we found that the digestion of non-biodegradable aminated, carboxylated, or unmodified fluorescent polystyrene NPs (PS-NPs) leads to different bioaccessible concentrations, with unmodified PS-NP concentrations being 3.5-and 4.5-fold lower than the aminated and carboxylated PS-NPs, respectively. In addition, we observed a reduced absorption of PS-NPs by ex vivo porcine intestinal tissue from the digestive matrix when compared to the absorption of their undigested counterparts in Krebs-Ringer Bicarbonate (KRB) buffer. The current results prove that oral absorption of PS-NPs in humans is to be expected in vivo. In the risk assessment of potential oral exposure to NPs in food products it is therefore key that the exposure and hazard assessment are performed with the NPs in physiologically relevant conditions, since this may influence the absorption and hazard properties of the NPs.

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Mucus thickness in the gastrointestinal tract of laboratory animals

Cited by 61 publications

References 68 publications

Oral uptake of nanoparticles: human relevance and the role of in vitro systems

Oral uptake of nanoparticles: human relevance and the role of in vitro systems

Mucus as a Barrier to Drug Delivery – Understanding and Mimicking the Barrier Properties

Prediction of Oral Absorption of Nanoparticles from Biorelevant Matrices Using a Combination of Physiologically Relevant In Vitro and Ex Vivo Models

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