PBPK-Compliant Human Intestine-Liver-Brain-Kidney Chip for Drug Development

Join Dr. Beren Atac Wagegg, Senior Scientist at TissUse GmbH, in a 37-minute webinar exploring groundbreaking developments in microphysiological systems for drug development. Discover how a novel PBPK-compliant ADME 4-Organ-Chip (Chip4) integrates intestinal barrier, liver microtissues, kidney models, and neuronal spheroids to recreate human tissue and organ-like functions at a 1:100,000 scale of the human body. Learn about the 14-day co-culture optimization process and examine the results of exposure tests using Haloperidol and Carbamazepine through various routes. Understand how this innovative research contributes to the development of in silico PBPK models for compound prediction, potentially reducing the need for laboratory animal testing while advancing preclinical insights at a systemic level.

Syllabus

Webinar Abstract: Microphysiological systems MPS have proven to be a powerful tool for recreating human tissue- and organ-like functions. However, establishing complex human in vitro ADME models involving co-culture of key organs to mimic physiologically based pharmacokinetic PBPK distribution behavior still present a challenge. In our recent study, we developed a PBPK compliant ADME 4-Organ-Chip Chip4 with a downscale factor of 0.000 of the human body. The integration of an intestinal barrier model for absorption and first-pass metabolism, liver microtissues for main metabolism, a kidney model with proximal tubular-like cells and podocytes for excretion, and neuronal spheroids as a potential target organ were optimized in the chip and co-cultured for 14 days. The setup was repeatedly exposed to Haloperidol, an antipsychotic medication and to Carbamazepine, a tricyclic compound with anticonvulsant properties through different routes. Results on direct as well as metabolite induced effects on organ-specific levels will be presented. Subsequently this data formed the basis for the development of an in silico PBPK model for compound prediction.