Abstract
Drugs affect the human body through absorption, distribution, metabolism, and elimination (ADME) processes. Due to their importance, the ADME processes need to be studied to determine the efficacy and side effects of drugs. Various in vitro model systems have been developed and used to realize the ADME processes. However, conventional model systems have failed to simulate the ADME processes because they are different from in vivo, which has resulted in a high attrition rate of drugs and a decrease in the productivity of new drug development. Recently, a microtechnology-based in vitro system called “organ-on-a-chip” has been gaining attention, with more realistic cell behavior and physiological reactions, capable of better simulating the in vivo environment. Furthermore, multi-organ-on-a-chip models that can provide information on the interaction between the organs have been developed. The ultimate goal is the development of a “body-on-a-chip”, which can act as a whole body model. In this review, we introduce and summarize the current progress in the development of multi-organ models as a foundation for the development of body-on-a-chip.
Highlights
Drugs are characterized by their pharmacokinetic (PK) and pharmacodynamic (PD) profiles [1,2,3]
Several challenges remain in the organ-on-a-chip-based field, which include the issue of cell culture medium and the correct down scaling of the chip to represent the human body
The MOC should be correctly designed, based on the relative size of each organ and the flow rate to reflect their physiological state inside the body
Summary
Drugs are characterized by their pharmacokinetic (PK) and pharmacodynamic (PD) profiles [1,2,3]. The ability to accurately predict the PK-PD profile in the early stages of drug development can reduce the failure rate of the development process [4]. Inaccurate predictions can result in toxicity or low efficacy, which is a major factor in the failure of new drug candidates [6]. In order to aid the drug development process, mathematical model-based PK-PD profiling has been developed and used [8]. PK-PD models were developed to overcome these issues [9], but because conventional cell culture models are used for PK-PD models, the predictions still widely differ from the in vivo results [9]. Improved in vitro prediction models are required for an accurate prediction of the efficacy of a drug following administration into the body [2]. We discuss and suggest future guidance for the development of a general body model
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