Evaluation of two dynamic in vitro models simulating fasted and fed state conditions in the upper gastrointestinal tract (TIM-1 and tiny-TIM) for investigating the bioaccessibility of pharmaceutical compounds from oral dosage forms

Verwei, Miriam; Minekus, Mans; Zeijdner, Evelijn; Schilderink, Ronald; Havenaar, R.

doi:10.1016/j.ijpharm.2015.11.048

Cited by 95 publications

(80 citation statements)

References 34 publications

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“…TIM Tiny-TIM [23] is a validated dynamic in vitro system that can be used for the determination of the true ileal (protein) digestibility and bioaccessibility. During the experiments, the digested and dissolved molecules are dialyzed from the intestinal lumen through a semipermeable membrane unit connected to the small intestinal compartment.…”

Section: Methodsmentioning

confidence: 99%

Non-targeted and targeted analysis of collagen hydrolysates during the course of digestion and absorption

Kleinnijenhuis¹,

Holthoon²,

Maathuis³

et al. 2019

Anal Bioanal Chem

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Protein hydrolysates are an important part of the human diet. Often, they are prepared from milk, soy, or collagen. In the present study, four different collagen hydrolysates were tested, varying in the average molecular weight and the animal source. Three types of samples, the dissolved start products, in vitro generated dialysates (containing the digested components that are potentially available for small intestinal absorption), and human serum collected after product ingestion, were analyzed using LC-MS to compare the state of the hydrolysates before and after absorption, i.e., uptake into the blood. It was found that the composition of the collagen hydrolysates prior to and after ingestion was highly complex and dynamic, which made it challenging to predefine a strategy for a targeted analysis. Therefore, we implemented a new analytical approach to first map hydrolysate data sets by performing non-targeted LC-MS analysis followed by non-targeted and targeted data analysis. It was shown that the insight gained by following such a top down (data) analytical workflow could be crucial for defining a suitable targeted setup and considering data trends beyond the defined targets. After having defined and performed a limited targeted analysis, it was found that, in our experimental setup, Hyp-Gly and especially Pro-Hyp contributed significantly as carrier to the total Hyp increase in blood after ingestion of collagen hydrolysate.

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Section: Methodsmentioning

confidence: 99%

Non-targeted and targeted analysis of collagen hydrolysates during the course of digestion and absorption

Kleinnijenhuis¹,

Holthoon²,

Maathuis³

et al. 2019

Anal Bioanal Chem

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“…In general, digestion models have been developed to predict i) the release of chemicals from a formulation (dissolution of medicines) (Cascone et al, 2016;Klein, 2010), ii) the release of chemicals from a complex matrix (i.e., bioaccessibility) (Oomen et al, 2003;Versantvoort et al, 2005) or iii) predicting digestion of macronutrients (e.g., Kopf-Bolanz et al, 2012). However, digestion methods are also increasingly used to study the stability of chemicals in the presence of digestive enzymes and the gastro-intestinal pH (e.g., Islam et al, 2014;Peters et al, 2012;Walczak et al, 2015aWalczak et al, , 2012 and in some cases the breakdown by microbiota (Verwei et al, 2016). New types of dynamic models that are gaining increasing attention are microfluidic gut-on-a-chip models, which provide the potential to develop protocols where in vitro cellular models for absorption harbour intestinal microbiota.…”

Section: In Vitro Methods For Luminal Degradation (By Digestive Enzymmentioning

confidence: 99%

Non-animal approaches for toxicokinetics in risk evaluations of food chemicals

Punt

2017

ALTEX

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Section: In Vitro Macromodelsmentioning

confidence: 99%

Models of the Gut for Analyzing the Impact of Food and Drugs

Fois

Schindeler

et al. 2019

Adv Healthcare Materials

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The human intestine is the primary organ responsible for the uptake of nutrients and water, and this is facilitated by its complex structure that features a large surface area. With an average total length of around seven meters, including both small and large intestine, it connects the stomach to the rectum while enabling absorption in a specialized manner. At a cellular level, the gut epithelium is critical in selective transport to the bloodstream. The finger-like projections of the intestinal epithelium Models of the human gastrointestinal tract (GIT) can be powerful tools for examining the biological interactions of food products and pharmaceuticals. This can be done under normal healthy conditions or using models of disease-many of which have no curative therapy. This report outlines the field of gastrointestinal modeling, with a particular focus on the intestine. Traditional in vivo animal models are compared to a range of in vitro models. In vitro systems are elaborated over time, recently culminating with microfluidic intestines-on-chips (IsOC) and 3D bioengineered models. Macroscale models are also reviewed for their important contribution in the microbiota studies. Lastly, it is discussed how in silico approaches may have utility in predicting and interpreting experimental data. The various advantages and limitations of the different systems are contrasted. It is posited that only through complementary use of these models will salient research questions be able to be addressed.

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Evaluation of two dynamic in vitro models simulating fasted and fed state conditions in the upper gastrointestinal tract (TIM-1 and tiny-TIM) for investigating the bioaccessibility of pharmaceutical compounds from oral dosage forms

Cited by 95 publications

References 34 publications

Non-targeted and targeted analysis of collagen hydrolysates during the course of digestion and absorption

Non-targeted and targeted analysis of collagen hydrolysates during the course of digestion and absorption

Non-animal approaches for toxicokinetics in risk evaluations of food chemicals

Models of the Gut for Analyzing the Impact of Food and Drugs

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