Physical and barrier changes in gastrointestinal mucus induced by the permeation enhancer sodium 8-[(2-hydroxybenzoyl)amino]octanoate (SNAC)

Mortensen, Janni Støvring; Bohr, Søren S.-R.; Rønholt, Stine; Hatzakis, Nikos S.; Saaby, Lasse; Nielsen, Hanne Mørck

doi:10.1016/j.jconrel.2022.09.034

Cited by 11 publications

(13 citation statements)

References 60 publications

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“…The fraction of freely moving NPs (i.e., exhibiting movement similar to that in buffer 20 ) decreased with increasing postnatal age for term piglets, while for preterm piglets, it increased sevenfold with increasing postnatal age (5 days vs. 8 days) (Fig. 1 D).…”

Section: Resultsmentioning

confidence: 96%

“…1 A, B) led to altered barrier properties of neonatal mucus, we introduced 100–300 nm nanoparticles (NPs) to the mucus. Using a single particle tracking assay, we directly observed the spatiotemporal localization of individual NPs, gaining insights into their movement within mucus 20 , 25 . In this study, NPs were employed as a model compound for large pathogens due to their comparable size to pathogenic microbes, such as viruses and bacteria 26 .…”

Section: Resultsmentioning

confidence: 99%

“…4 A, G′ represents the amount of stored energy in the mucus network after deformation, whereas G″ represents the energy that has been lost after deformation. Hence, G′ can be related to the number of intermolecular interactions (i.e., elasticity) in the porous network of mucus, whereas the G″/G′ ratio (loss factor) represents the strength of these intermolecular interactions within the porous network of mucus 20 .

Figure 4 Rheological properties of ex vivo small intestinal mucus from 5-day old healthy piglets born with different birth maturities.…”

Section: Resultsmentioning

confidence: 99%

“…Though these dietary differences would in the clinical setting to cover the nutritional need of preterm, near-term and term infants. Intestinal mucus is known for its highly selective size filtration and interactive properties, which make passage through mucus highly dependent on the physicochemical properties of the permeating compound 20 , 28 , 32 , 33 . This may explain why mucus from preterm piglets exhibited both the slowest NP diffusion rates and the highest permeation of the small molecule and macromolecular model compounds compared to mucus from near-term and term piglets.…”

Section: Resultsmentioning

confidence: 99%

“…However, the exact mechanisms by which C10 enhances the barrier properties of the gastrointestinal tract remain unknown. A previous study has identified another medium-chain fatty acid that improves the barrier properties of intestinal mucus in pigs 20 , leading to speculation whether C10 might also enhance the neonatal mucus barrier, thus explaining the observed improvements in the gastrointestinal tract’s barrier function 18 , 19 .…”

Section: Introductionmentioning

confidence: 99%

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Neonatal intestinal mucus barrier changes in response to maturity, inflammation, and sodium decanoate supplementation

Mortensen,

Bohr,

Krog

et al. 2024

Sci Rep

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The integrity of the intestinal mucus barrier is crucial for human health, as it serves as the body's first line of defense against pathogens. However, postnatal development of the mucus barrier and interactions between maturity and its ability to adapt to external challenges in neonatal infants remain unclear. In this study, we unveil a distinct developmental trajectory of the mucus barrier in preterm piglets, leading to enhanced mucus microstructure and reduced mucus diffusivity compared to term piglets. Notably, we found that necrotizing enterocolitis (NEC) is associated with increased mucus diffusivity of our large pathogen model compound, establishing a direct link between the NEC condition and the mucus barrier. Furthermore, we observed that addition of sodium decanoate had varying effects on mucus diffusivity depending on maturity and health state of the piglets. These findings demonstrate that regulatory mechanisms governing the neonatal mucosal barrier are highly complex and are influenced by age, maturity, and health conditions. Therefore, our results highlight the need for specific therapeutic strategies tailored to each neonatal period to ensure optimal gut health.

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Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Figure 4 Rheological properties of ex vivo small intestinal mucus from 5-day old healthy piglets born with different birth maturities.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Neonatal intestinal mucus barrier changes in response to maturity, inflammation, and sodium decanoate supplementation

Mortensen,

Bohr,

Krog

et al. 2024

Sci Rep

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Defect‐Engineered Metal–Organic Frameworks as Nanocarriers for Pharmacotherapy: Insights into Intracellular Dynamics at The Single Particle Level

Huang,

Dreisler,

Kæstel‐Hansen

et al. 2024

Advanced Materials

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Nanoscale Metal‐Organic Frameworks (nanoMOFs) are widely implemented in a host of assays involving drug delivery, biosensing catalysis, and bioimaging. However, the cell pathways and cell fate remain poorly understood. Here, we have synthesized a new fluorescent nanoMOF integrating ATTO 655 into surface defects of colloidal UiO‐66, allowing us to track the spatiotemporal localization of Single nanoMOF in live cells. DFT reveals the stronger binding of ATTO 655 to the Zr6 cluster nodes compared with phosphate and Alendronate Sodium. Parallelized tracking of the spatiotemporal localization of thousands of nanoMOFs and analysis using machine learning platforms revealed whether nanoMOFs remain outside as well as their cellular internalization pathways. To quantitatively assess their colocalization with endo/lysosomal compartments, we developed a colocalization proxy approach relying on the nanoMOF detection of particles in one channel to the signal in the corresponding endo/lysosomal compartments channel, considering signal versus local background intensity ratio and signal‐to‐noise ratio. This strategy mitigates colocalization value inflation from high or low signal expression in endo/lysosomal compartments. The results accurately measure the nanoMOFs’ colocalization from early to late endosomes and lysosomes and emphasize the importance of understanding their intracellular dynamics based on single‐particle tracking for optimal and safe drug delivery.This article is protected by copyright. All rights reserved

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Effects of prophylactic antibiotics administration on barrier properties of intestinal mucosa and mucus from preterm born piglets

Mortensen

Nguyen

Nielsen

et al. 2023

Drug Deliv. and Transl. Res.

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Physical and barrier changes in gastrointestinal mucus induced by the permeation enhancer sodium 8-[(2-hydroxybenzoyl)amino]octanoate (SNAC)

Cited by 11 publications

References 60 publications

Neonatal intestinal mucus barrier changes in response to maturity, inflammation, and sodium decanoate supplementation

Neonatal intestinal mucus barrier changes in response to maturity, inflammation, and sodium decanoate supplementation

Defect‐Engineered Metal–Organic Frameworks as Nanocarriers for Pharmacotherapy: Insights into Intracellular Dynamics at The Single Particle Level

Effects of prophylactic antibiotics administration on barrier properties of intestinal mucosa and mucus from preterm born piglets

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