Cytotoxicity Assay: Evaluating Drug Safety and Cell Proliferation
Cytotoxicity assays are developed to analyze the ability of certain drug compounds to destroy the healthy cells of an organism. Cytotoxic compounds can lead to accidental cell death (referred to as necrosis) or programmed cell death (referred to as apoptosis). During the nonclinical and clinical research phases of drug discovery and development, cytotoxicity assays assess the safety profile of the drug candidate. The method proves valuable in identifying off-target effects of certain drug compounds on the human body.
For drug compounds developed for cancer treatment, cytotoxicity assays are critical in a variety of testing activity. Compounds that can hinder or stop cell proliferation make strong anti-cancer candidates.
Multiple cytotoxicity assays are used to assess different cell functions such as cell membrane permeability, enzyme activity, ATP production, cell adherence, nucleotide uptake, and co-enzyme production. Cytotoxicity assay should be selected based on the drug compound and with careful consideration of cellular function. The most effective method for assessment of cytotoxicity of the drug compound is evaluating cell membrane integrity. Cells having cytotoxic effects often show signs of compromised membrane integrity.
Cytotoxicity Assay: From Drug Discovery and Preclinical to Clinical Phases
Every new drug candidate is continuously subjected to extensive tests for safety and efficacy before approval. Cytotoxicity testing is one way to test the safety of a drug on target and off-target cells in early stages of drug development. Toxicity testing for on- and off-target effects is necessary for safe drug administration.
In vitro assessments establish the toxicity of a drug compound in the human body. The permeability, metabolic stability, and interactions to membrane transporter systems are assessed in cell models relevant to the human body. A safety profile is achieved by combining cytotoxicity assay testing with in vivo tests of absorption, distribution, metabolism, and excretion.
Although cytotoxicity assays aim at finding toxicity of the drug compound or sample compound, it is unlikely to assess toxicity with a single test accurately. Multiple screening models are used for cell viability assessments in various human cell lines.