Role of Extracellular Vesicle-Derived Biomarkers in Drug Metabolism and Disposition

Extracellular vesicles (EVs) are small, nonreplicating, lipid-encap-sulated particles that contain a myriad of protein and nucleic acid cargo derived from their tissue of origin. The potential role of EV-derived biomarkers to the study of drug metabolism and disposi-tion (DMD) has gained attention in recent years. The key trait that makes EVs an attractive biomarker source is their capacity to pro-vide comparable insights to solid organ biopsy through an appre-ciably less invasive collection procedure. Blood-derived EVs exist as a heterogenous milieu of biologically distinct particles originat-ing from different sources through different biogenesis pathways. Furthermore, blood (plasma and serum) contains an array of vesic-ular and nonvesicular contaminants, such as apoptotic bodies, plasma proteins, and lipoproteins that are routinely coisolated with EVs, albeit to a different extent depending on the isolation tech-nique. The following minireview summarizes current studies reporting DMD biomarkers and addresses elements of EV isolation 2021; accepted July 28, 2021 and quantification relevant to the application of EV-derived DMD biomarkers. Evidence based-best practice guidance aligned to Minimum Information for the Study of Extracellular Vesicles and EV-TRACK reporting standards are summarized in the context of DMD studies.