TY - JOUR
T1 - Dynamic colon model (DCM)
T2 - a cine-mri informed biorelevant in vitro model of the human proximal large intestine characterized by positron imaging techniques
AU - Stamatopoulos, Konstantinos
AU - Karandikar, Sharad
AU - Goldstein, Mark
AU - O’Farrell, Connor
AU - Marciani, Luca
AU - Sulaiman, Sarah
AU - Hoad, Caroline L.
AU - Simmons, Mark J. H.
AU - Batchelor, Hannah K.
PY - 2020/7/13
Y1 - 2020/7/13
N2 - 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.
AB - 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.
KW - cine-MRI
KW - colon motility
KW - colon-specific drug formulations
KW - dissolution
KW - dynamic colon model (DCM)
KW - in vitro models
KW - magnetic resonance imaging (MRI)
KW - positron emission tomography (PET)
UR - http://www.scopus.com/inward/record.url?scp=85087980882&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics12070659
DO - 10.3390/pharmaceutics12070659
M3 - Article
AN - SCOPUS:85087980882
SN - 1999-4923
VL - 12
JO - Pharmaceutics
JF - Pharmaceutics
IS - 7
M1 - 659
ER -