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Extracellular Vesicles as Surrogates for Drug Metabolism and Clearance: Promise vs. Reality

Drug-metabolizing enzymes (DMEs) and transporters play a major role in drug efficacy and safety. They are regulated at multiple levels and by multiple factors. Estimating their expression and activity could contribute to predicting drug pharmacokinetics and their regulation by drugs or pathophysiolo...

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Autores principales: Gagliardi, Anna, Bajraktari-Sylejmani, Gzona, Barocelli, Elisabetta, Weiss, Johanna, Rigalli, Juan Pablo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10455864/
https://www.ncbi.nlm.nih.gov/pubmed/37629602
http://dx.doi.org/10.3390/life13081745
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author Gagliardi, Anna
Bajraktari-Sylejmani, Gzona
Barocelli, Elisabetta
Weiss, Johanna
Rigalli, Juan Pablo
author_facet Gagliardi, Anna
Bajraktari-Sylejmani, Gzona
Barocelli, Elisabetta
Weiss, Johanna
Rigalli, Juan Pablo
author_sort Gagliardi, Anna
collection PubMed
description Drug-metabolizing enzymes (DMEs) and transporters play a major role in drug efficacy and safety. They are regulated at multiple levels and by multiple factors. Estimating their expression and activity could contribute to predicting drug pharmacokinetics and their regulation by drugs or pathophysiological situations. Determining the expression of these proteins in the liver, intestine, and kidney requires the collection of biopsy specimens. Instead, the isolation of extracellular vesicles (EVs), which are nanovesicles released by most cells and present in biological fluids, could deliver this information in a less invasive way. In this article, we review the use of EVs as surrogates for the expression and activity of DMEs, uptake, and efflux transporters. Preliminary evidence has been provided for a correlation between the expression of some enzymes and transporters in EVs and the tissue of origin. In some cases, data obtained in EVs reflect the induction of phase I-DMEs in the tissues. Further studies are required to elucidate to what extent the regulation of other DMEs and transporters in the tissues reflects in the EV cargo. If an association between tissues and their EVs is firmly established, EVs may represent a significant advancement toward precision therapy based on the biotransformation and excretion capacity of each individual.
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spelling pubmed-104558642023-08-26 Extracellular Vesicles as Surrogates for Drug Metabolism and Clearance: Promise vs. Reality Gagliardi, Anna Bajraktari-Sylejmani, Gzona Barocelli, Elisabetta Weiss, Johanna Rigalli, Juan Pablo Life (Basel) Review Drug-metabolizing enzymes (DMEs) and transporters play a major role in drug efficacy and safety. They are regulated at multiple levels and by multiple factors. Estimating their expression and activity could contribute to predicting drug pharmacokinetics and their regulation by drugs or pathophysiological situations. Determining the expression of these proteins in the liver, intestine, and kidney requires the collection of biopsy specimens. Instead, the isolation of extracellular vesicles (EVs), which are nanovesicles released by most cells and present in biological fluids, could deliver this information in a less invasive way. In this article, we review the use of EVs as surrogates for the expression and activity of DMEs, uptake, and efflux transporters. Preliminary evidence has been provided for a correlation between the expression of some enzymes and transporters in EVs and the tissue of origin. In some cases, data obtained in EVs reflect the induction of phase I-DMEs in the tissues. Further studies are required to elucidate to what extent the regulation of other DMEs and transporters in the tissues reflects in the EV cargo. If an association between tissues and their EVs is firmly established, EVs may represent a significant advancement toward precision therapy based on the biotransformation and excretion capacity of each individual. MDPI 2023-08-14 /pmc/articles/PMC10455864/ /pubmed/37629602 http://dx.doi.org/10.3390/life13081745 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Gagliardi, Anna
Bajraktari-Sylejmani, Gzona
Barocelli, Elisabetta
Weiss, Johanna
Rigalli, Juan Pablo
Extracellular Vesicles as Surrogates for Drug Metabolism and Clearance: Promise vs. Reality
title Extracellular Vesicles as Surrogates for Drug Metabolism and Clearance: Promise vs. Reality
title_full Extracellular Vesicles as Surrogates for Drug Metabolism and Clearance: Promise vs. Reality
title_fullStr Extracellular Vesicles as Surrogates for Drug Metabolism and Clearance: Promise vs. Reality
title_full_unstemmed Extracellular Vesicles as Surrogates for Drug Metabolism and Clearance: Promise vs. Reality
title_short Extracellular Vesicles as Surrogates for Drug Metabolism and Clearance: Promise vs. Reality
title_sort extracellular vesicles as surrogates for drug metabolism and clearance: promise vs. reality
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10455864/
https://www.ncbi.nlm.nih.gov/pubmed/37629602
http://dx.doi.org/10.3390/life13081745
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