Methods for simulating and modeling alimentary tract conditions and processes

There are a number of alimentary tract model systems available applying different physical models (e.g flasks and sequential solution approximations of alimentary tract lumen), cell types (e.g. Caco-2, T84, HT29, IEC (rat), FRIC-B (rat)), and co-culture models such as CacoGoblet and CacoReady. There are also different type of culture systems and conditions/media that should be considered.

The charge of Task Group 3 was as follows, with respect to model evaluation for nanoparticles:

    1. Consider models or evaluation methods for total absorption (e.g., uptake vs excretion)
    2. Provide an overview the possible translocation mechanisms of nanoparticles from the gut to the systemic circulation. (coordinated with Task Group 2)
    3. Provide an overview of gut model systems that are used for or may be suitable for nanomaterials, including 3D systems and identify the most promising system/systems considering the range of different environments along the gut. Is there a specific gut region that is more sensitive and therefore more suitable to target? Discuss if specific cell clones are more suitable than others, and issues related to species extrapolation for models applying animal cell lines. Are there models available for diseased/disturbed guts that could be suitable or more sensitive? Discuss also time and resources required and the possibility to use methods in high throughput systems.
    4. Discuss nanospecific considerations and adaptations that are required to reduce interference (e.g. precipitation, binding to membranes) and optimise the gut models for nanomaterials (e.g. assuring nanomaterials are being presented to the cells, co-culturing of cell types, presence of mucous, mechanical movement).
    5. Are there nanospecific effects that influence the gut microflora that may have effect on the translocation. (coordinate with Task Group 2)
    6. Provide and discuss suitable methods for detection of nanomaterials present and released in gut model (NR) conditions. Discuss suitable positive and negative controls