Advanced In Vitro Models for Preclinical Drug Safety: Recent Progress and Prospects

Area of Science:

• Biomedical Engineering
• Pharmacology
• Toxicology

Background:

• Drug development is lengthy and costly, with drug-induced liver injury (DILI) posing a significant challenge.
• Current preclinical models (animal and in vitro) poorly predict human DILI due to physiological differences.
• This leads to high failure rates in clinical trials and increased development costs.

Purpose of the Study:

• To review the significance, current status, and future prospects of advanced in vitro platforms for preclinical drug discovery.
• To highlight the potential of organ-on-a-chip (OOC) models in addressing DILI prediction challenges.
• To discuss how OOC technologies can accelerate drug approval while adhering to the 3Rs principles.

Main Methods:

• Review of current literature on organ-on-a-chip technologies in drug development.
• Focus on gut-liver-on-a-chip models as advanced in vitro systems.
• Discussion of the application of these platforms in assessing drug efficacy and toxicity.

Main Results:

• Organ-on-a-chip models, particularly gut-liver-on-a-chip systems, closely mimic human physiology.
• These advanced models show potential for improved prediction of DILI compared to traditional methods.
• Successful adaptation of OOC technology can enhance drug efficacy and minimize toxicity.

Conclusions:

• Organ-on-a-chip models are crucial for improving the accuracy of DILI risk assessment in preclinical drug discovery.
• These technologies offer a pathway to reduce drug development timelines and costs.
• OOC platforms support the 3Rs principles (replacement, reduction, refinement) in animal testing.