Dynamic colon model (DCM): a cine-mri informed biorelevant in vitro model of the human proximal large intestine characterized by positron imaging techniques

Konstantinos Stamatopoulos, Sharad Karandikar, Mark Goldstein, Connor O’Farrell, Luca Marciani, Sarah Sulaiman, Caroline L. Hoad, Mark J. H. Simmons, Hannah K. Batchelor

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Abstract

This work used in vivo MRI images of human colon wall motion to inform a biorelevant Dynamic Colon Model (DCM) to understand the interplay of wall motion, volume, viscosity, fluid, and particle motion within the colon lumen. Hydrodynamics and particle motion within the DCM were characterized using Positron Emission Tomography (PET) and Positron Emission Particle Tracking (PEPT), respectively. In vitro PET images showed that fluid of higher viscosity follows the wall motion with poor mixing, whereas good mixing was observed for a low viscosity fluid. PEPT data showed particle displacements comparable to the in vivo data. Increasing fluid viscosity favors the net forward propulsion of the tracked particles. The use of a floating particle demonstrated shorter residence times and greater velocities on the liquid surface, suggesting a surface wave that was moving faster than the bulk liquid. The DCM can provide an understanding of flow motion and behavior of particles with different buoyancy, which in turn may improve the design of drug formulations, whereby fragments of the dosage form and/or drug particles are suspended in the proximal colon.

Original languageEnglish
Article number659
Number of pages20
JournalPharmaceutics
Volume12
Issue number7
DOIs
Publication statusPublished - 13 Jul 2020

Keywords

  • cine-MRI
  • colon motility
  • colon-specific drug formulations
  • dissolution
  • dynamic colon model (DCM)
  • in vitro models
  • magnetic resonance imaging (MRI)
  • positron emission tomography (PET)

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