Validation study
Validating TIM Cell: Bridge the gap between bioaccessibility & absorption
Permeability testing closer to physiological conditions
The unique combination of TIM® biorelevant fluids and TIM Cell was validated using two BCS Class IV compounds (furosemide and chlorothiazide) characterized by poor aqueous solubility and low membrane permeability.
Caco-2 cells were cultured under dynamic millifluidic conditions using organ-on-a-chip MIVO® technology by React4life and differentiated on an extracellular matrix. A human-like intestinal mucous layer was added to better mimic the intestinal barrier. Barrier integrity was monitored via transepithelial electrical resistance (TEER) measurements and FITC-dextran permeability assays.
Keywords
The results
- Moving from static to dynamic culture conditions reduced cell differentiation time from 21 days to 10.
- Culturing Caco-2 cells on a physiological extracellular matrix combined with the human-like mucous layer, protected cells from the cytotoxicic effects of biorelevant fluids.
- Furosemide and Chlorothiazide measured in TIM Cell was in agreement with in vivo human fraction absorbed (Fa).
- Negative food effect of Furosemide was demonstrated by TIM Cell
TIM Cell predicts intestinal permeability in TIM® intestinal fluids, enabling more confident ranking of oral drugs and nutraceuticals.
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