Table of Contents:

Biochemistry

Dynamic digestion models, like static models, are built to mimic the biochemical environment of the compartments of the GI tract. Many of the considerations highlighted in the earlier sections of this chapter therefore apply to dynamic models as well: What concentrations of which enzymes, bile salts and phospholipids should be used? Can porcine, bovine or fungal versions of enzymes be used? Is it better to use complex mixtures (e.g. pancreatin) or individual, purified enzymes? At what pH should digestion take place? How long should a given meal reside in the stomach?

In contrast to static models, however, the exact conditions within the different compartments of a dynamic model will change over time to simulate the in vivo digestion processes. Dynamic digestion models generally have a number of different digestive secretions which are added to the compartments of the model over time. This addition can either follow a steady secretion rate (e.g. the simulated gastric juice of HGS is added at a rate of 2.5 mL/min), or it can follow a pre-programmed pattern allowing the rate to change over time (e.g. in the TIM-1 model), or it can be programmed to change in response to other parameters, such as the fill volume of the model (e.g. gastric secretion in the DGM). The pH is often monitored in real-time within dynamic models and is used to control the rate of addition of hydrochloric acid, allowing the acidification of the meal within the gastric compartment to follow a pre-determined curve. In dynamic models which incorporate a duodenal step, at this stage the pH of the chyme is neutralized by controlled addition of sodium bicarbonate solution, and secretions of bile and pancreatic enzymes (or pancreatin) are added.

Whilst the concentrations of enzymes, bile, electrolytes and phospholipids are set for the various secretions used in dynamic models, the concentrations of these components within the digesta cannot be readily determined. This is in part due to the dynamic nature of the models, allowing secretion rates to change throughout the digestion process. However, it is also due to the inhomogeneity of the bolus within the models. In vivo, a solid meal will be ingested over a period of time as small balls of chewed food. Within the fundus of the stomach, the bolus is only subjected to gentle contractions and therefore is not well mixed. Whilst the outside of the bolus is acted upon by gastric secretions, it can take over 1 h for these secretions to penetrate to the center of the bolus (Marciani et al. 2001b). In the antral part of the stomach, strong peristaltic waves mix the bolus more readily, producing a more homogeneous chyme.

Some of the more advanced dynamic digestion models have a geometry designed to represent the fundus and antrum of the stomach, and/or the duodenum. These designs allow for the simulation of the physical forces exerted on the digesta during transit through the GI tract, which in turn allows for simulation of the inhomogeneous nature of digesta and localized biochemical environments, as in vivo.

References

Campbell G, Arcand Y, Mainville I (2011) Development of a tissue mimicking stomach construct for in-vitro digestive system. Paper presented at the plant bioactives research in Canada. Canada-United Kingdom Gut and Health Workshop, Saint-Hyacinthe, QC, Canada, 24–25 February 2011

Kong FB, Singh RP (2010) A human gastric simulator (HGS) to study food digestion in human stomach. J Food Sci 75(9):E627–E635. doi:10.1111/j.1750-3841.2010.01856.x

Marciani L, Gowland PA, Fillery-Travis A, Manoj P, Wright J, Smith A, Young P, Moore R, Spiller RC (2001a) Assessment of antral grinding of a model solid meal with echo-planar imaging. Am J Physiol Gastrointest Liver Physiol 280(5):G844–G849

Marciani L, Gowland PA, Spiller RC, Manoj P, Moore RJ, Young P, Fillery-Travis AJ (2001b) Effect of meal viscosity and nutrients on satiety, intragastric dilution, and emptying assessed by MRI. Am J Physiol Gastrointest Liver Physiol 280(6):G1227–G1233

Tompkins TA, Mainville I, Arcand Y (2011) The impact of meals on a probiotic during transit through a model of the human upper gastrointestinal tract. Benef Microbes 2(4):295–303. doi:10.3920/Bm2011.0022

Vardakou M, Mercuri A, Barker SA, Craig DQM, Faulks RM, Wickham MSJ (2011) Achieving antral grinding forces in biorelevant in vitro models: comparing the USP dissolution apparatus II and the dynamic gastric model with human in vivo data. AAPS PharmSciTech 12(2):620– 626. doi:10.1208/s12249-011-9616-z

 
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