Evaluation of active substances and drugs in vitro - cell models and selected assays

Abstract

Intensive search for new drugs necessitates the development of quick and reliable methods for their evaluation. These methods, already at the stage of laboratory tests, are intended to allow obtaining the broadest possible knowledge about the mechanisms of action, absorption and transport of the drug, determine its therapeutic concentration, half-life and metabolism, and should be repeatable and relatively cheap. Currently, almost all processes important in the context of the effectiveness of therapy can be assessed based on tissue and cell cultures. It is possible not only to keep any cells alive, but also to construct spatial cultures where the interactions of cells with each other – just like in vivo – are multidirectional. Improving and refining the methods of cultivating human cells - from highly differentiated cells to stem cells - allows for the creation of a research model that largely reproduces most of the processes occurring in the body and reflects the relationships there. Additionally, research conducted in vitro enables simultaneous determinations in various aspects of drug evaluation and indication of which specific cells and structures within a given organ and organism the tested substance has an effect on. Simple methods have become widely available for assessing the cytotoxicity and genotoxicity of compounds, selecting optimal concentrations of test substances with respect to their effects on selected cells and organs, assessing changes at the molecular level, transport across membranes, and finally drug biotransformation processes. Assessment of the drug in terms of LADME (liberation, absorption, distribution, metabolism, excretion) - the processes to which each drug is subjected in the body can be almost entirely carried out in laboratory conditions. The results obtained in vitro are important both in terms of general knowledge about the action of a given drug and for determining the directions of development of technology for obtaining the most effective form of a drug, and the possibility of analysis in the context of the patient's individual conditions opens a new path - the implementation of personalized therapy. The aim of the work was to present the reader with increasing possibilities in this area and to show the enormous progress that has been made in recent years in extracorporeal research models mapping the course of the body’s reaction to a potential drug or other xenobiotics. The authors also wanted to show and compare information on new, in their own way very complicated, but also simple in their concept, in vitro models, with specific assays used (both for 2D and 3D cultures) to assess the effect of a drug or other xenobiotic on cells in cultures – thus indicating that these are not inaccessible methods and technologies that could not be introduced into most of the laboratories already operating today.

Keywords

• in vitro
• evaluation of the drug
• 3d cell cultures
• toxicology evaluation