Validation study

Validating TIM Cell: Bridge the gap between bioaccessibility & absorption

 

 

About the project

Conventional permeability assays use simplified buffer systems that fail to capture the complex intestinal environment. When drugs are administered to the TIM® systems at clinically relevant doses, drugs are exposed to physiologically accurate intestinal fluids, containing bile salts, phospholipids, enzymes and digestion products, and both free and micelle-bound solubilized drug. Samples collected from the TIM® lumen could be used for highly biorelevant permeability assays, particularly for drugs with poor solubility and permeability. However, key components of these biorelevant fluids, such as bile salts, are cytotoxic when applied to traditional Caco-2 monolayers, the gold-standard for permeability assays, limiting their use.

TIM Cell was developed to bridge the gap between bioaccessibility and absorption and bring permeability testing closer to physiological conditions

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.

 

 

 

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
Contact us for all details

TIM Cell predicts intestinal permeability in TIM® intestinal fluids, enabling more confident ranking of oral drugs and nutraceuticals. 

Tania Garcia, PhD Manager at InnoGI Technologies

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We are excited to hear what’s on your plate and how we can help you understand what happens to your product during digestion!

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