Introduction
Drug development has always posed the strict challenge of having to test the drug candidates for safety and efficacy before they hit the market. While animal testing and cell cultures in vitro have earned invaluable information from the research, they usually fail in the prediction of human responses. Consequently, many drugs that seemed safe in preclinical models have caused adverse effects in human trials, with sometimes fatal results. This gulf between preclinical testing and clinical outcome has driven the search for more reliable models that are relevant to humans. Microphysiological systems (MPS), or organs-on-chips, These sophisticated in vitro models develop a paradigm shift in drug safety testing as they can model the complex physiological environments of tissues and organs in the human body. This is because MPS presents an opportunity to integrate several organ systems into a single platform with the goal of bridging the gap between preclinical studies and human clinical trials. It charts a course for more accurate and predictive preclinical assessment in toxicology.
Traditional drug safety testing has limitations
Testing for safety in drugs has traditionally relied on animal models and two-dimensional cell cultures. Such methods have contributed a great deal of information, but these traditional methods have some inherent limitations. Animal models are considered the gold standard for all preclinical tests, but they quite frequently fail in the prediction of human-specific responses because of interspecies differences in metabolism, genetics, and physiology. For instance, drugs that are safe for rodents or other animals are sometimes, in a very toxic way, human toxicants. This occurs at a great expense in terms of money and time when drug development has to be rolled back.
Furthermore, 2D cell cultures miss the 3D architecture with complex cellular interactions of human tissues, something as simple as growing cells in a flat monolayer. This limitation frequently leads to an oversimplification of human biology and thus predicts the wrong drug efficacy and toxicity. Correspondingly, there has been a general recognition that more advanced models that better mimic human physiology are needed.
The Emergence of Microphysiological Systems
One of the successful resolutions toward the drawbacks of traditional drug testing methods is microphysiological systems, otherwise referred to as organs-on-chips. These devices make use of microfluidic technology to create miniature versions of human organs that house multiple cell types and recreate 3D architecture with mechanical forces similar to those in vivo. In this respect, MPS can model the dynamic environment of human tissue to better determine drug effects.
Another advantage of MPS is the complex modeling of organ function and interaction within a controlled environment. For instance, a liver-on-chip can model the metabolic functions of the liver, thus providing an understanding of how a drug is processed and metabolized inside the human body. There has been a heart-on-chip designed that imitates the mechanical and electrical activities of the heart, allowing the in vitro study of drug-induced cardiotoxicity.
Moreover, by binding various organ systems into a single platform, MPS enables the appreciation of kinetics between highly disparate tissues and organs, thereby finally furnishing an integrated view of the action of the tested compound. This is very important for the detection of drug interactions and off-target effects, which commonly cannot be determined by conventional testing models.