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- air-liquid interface (1)
- artificial membrane-permeability (1)
- asthmatic bronchial epithelium (1)
- blood-brain barrier (BBB) model (1)
- brain–liver chip (1)
- cytotoxicity (1)
- embryonic stem cells (1)
- epithelial cell culture (1)
- human induced pluripotent stem cells (hiPSCs) (1)
- in vitro models (1)
- microphysiological systems (MPS) (1)
- multi-organ chip (1)
- on-a-chip (1)
- permeability (1)
- pulmonary drug-delivery (1)
- reconstructed human epidermis (1)
- respiratory syncytial virus (1)
- transport studies (1)
- vesicle-based barrier (1)
Significant advancements in the field of preclinical in vitro blood-brain barrier (BBB) models have been achieved in recent years, by developing monolayer-based culture systems towards complex multi-cellular assays. The coupling of those models with other relevant organoid systems to integrate the investigation of blood-brain barrier permeation in the larger picture of drug distribution and metabolization is still missing. Here, we report for the first time the combination of a human induced pluripotent stem cell (hiPSC)-derived blood-brain barrier model with a cortical brain and a liver spheroid model from the same donor in a closed microfluidic system (MPS). The two model compounds atenolol and propranolol were used to measure permeation at the blood–brain barrier and to assess metabolization. Both substances showed an in vivo-like permeation behavior and were metabolized in vitro. Therefore, the novel multi-organ system enabled not only the measurement of parent compound concentrations but also of metabolite distribution at the blood-brain barrier.