Lymphatic absorption of lipophilic particles and macromolecules provides a pathway for orally administrated lipophilic small molecule drugs to circumvent hepatic metabolism and enhance drug exposure. Yet, there haven’t been representative models to study the interaction between the intestinal epithelium and local lymphatic system to optimize the uptake of these lipophilic drugs and evaluate their absorption and potential toxicity. In this study, I will develop a representative model of the intestinal-lymphatic interaction and immune responses in a microfluidic setup. The uptake of lipophilic drugs is facilitated through the absorption of dietary lipids, namely by active transport on the apical side and chylomicron secretion on the basal side of enterocytes. Therefore, the transport of lipids and subsequently lipophilic particles across the intestinal cells will be evaluated by LC/MS, UPLCS and ELISA assays. Then, the intestinal and lymphatic model will be combined with immune cells to evaluate the local immune response to the administrated drugs. Moreover, cytokines and pathogen-derived ligands will be introduced to simulate an inflamed intestine and investigate its effect on intestinal permeability, cell toxicity, and cytokine release of intestinal and immune cells.
|Effective start/end date||1/05/22 → …|
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