The AAPS Journal High Impact Article Award was presented at the 2019 AAPS PharmSci 360.
The 2019 AAPS Journal High Impact Article Award was presented to Murat Cirit, Nikolaos Tsamandouras, Wen Li, Kelly Chen, Collin D. Edington, Cynthia L. Stokes, and Linda G. Griffith for their article Integrated Gut and Liver Microphysiological Systems for Quantitative In Vitro Pharmacokinetic Studies. This open access research article was published in July 2017. It has received more than 3,500 downloads and 32 citations (as of November 2019).
Abstract
Investigation of the pharmacokinetics (PK) of a compound is of significant importance during the early stages of drug development, and therefore several in vitro systems are routinely employed for this purpose. However, the need for more physiologically realistic in vitro models has recently fueled the emerging field of tissue-engineered 3D cultures, also referred to as organs-on-chips, or microphysiological systems (MPSs). We have developed a novel fluidic platform that interconnects multiple MPSs, allowing PK studies in multi-organ in vitro systems along with the collection of high-content quantitative data. This platform was employed here to integrate a gut and a liver MPS together in continuous communication, and investigate simultaneously different PK processes taking place after oral drug administration in humans (e.g., intestinal permeability, hepatic metabolism). Measurement of tissue-specific phenotypic metrics indicated that gut and liver MPSs can be fluidically coupled with circulating common medium without compromising their functionality. The PK of diclofenac and hydrocortisone was investigated under different experimental perturbations, and results illustrate the robustness of this integrated system for quantitative PK studies. Mechanistic model-based analysis of the obtained data allowed the derivation of the intrinsic parameters (e.g., permeability, metabolic clearance) associated with the PK processes taking place in each MPS. Although these processes were not substantially affected by the gut-liver interaction, our results indicate that inter-MPS communication can have a modulating effect (hepatic metabolism upregulation). We envision that our integrative approach, which combines multi-cellular tissue models, multi-MPS platforms, and quantitative mechanistic modeling, will have broad applicability in pre-clinical drug development.
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New Pharmaceutical Research Editor
AAPS and Springer Nature welcome Tonglei Li, Ph.D., to the Pharmaceutical Research team as the upcoming editor-in-chief. Li will start his new role in July 2020. He is the Allen Chao Chair and Professor of Industrial and Physical Pharmacy at Purdue University, College of Pharmacy. His research areas include solid-state chemistry, computational chemistry, formulation, and drug delivery.
We thank Peter Swaan, Ph.D., University of Maryland, for his 10 years of service to the journal and AAPS. Swaan will be stepping down in June 2020. Look for more features on Li and Swaan later this year.