Journal Article Review Epublish 4 citations
PubMed: 39852122 DOI: 10.3390/cimb47010007
Advanced In Vitro Models for Preclinical Drug Safety: Recent Progress and Prospects.
Curr Issues Mol Biol 47(1)
Authors: Dileep G Nair, Ralf Weiskirchen
Affiliations
- Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), University Hospital Aachen, D-52074 Aachen, Germany. Keliomics Inc. 4640 S Macadam Ave #270, Portland, OR 97239, USA.
- Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), University Hospital Aachen, D-52074 Aachen, Germany.
Abstract
The majority of drugs are typically orally administered. The journey from drug discovery to approval is often long and expensive, involving multiple stages. A major challenge in the drug development process is drug-induced liver injury (DILI), a condition that affects the liver, the organ responsible for metabolizing most drugs. Traditionally, identifying DILI risk has been difficult due to the poor correlation between preclinical animal models and in vitro systems. Differences in physiology between humans and animals or cell lines contribute to the failure of many drug programs during clinical trials. The use of advanced in vitro systems that closely mimic human physiology, such as organ-on-a-chip models like gut-liver-on-a-chip, can be crucial in improving drug efficacy while minimizing toxicity. Additionally, the adaptation of these technologies has the potential to significantly reduce both the time and cost associated with obtaining safe drug approvals, all while adhering to the 3Rs principle (replacement, reduction, refinement). In this review, we discuss the significance, current status, and future prospects of advanced platforms, specifically organ-on-a-chip models, in supporting preclinical drug discovery.
MeSH
Physiology, Drug Discovery, Safety, Pharmaceutical Preparations, Liver, Induced Pluripotent Stem Cells