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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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/13/8/1745 |
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| author | Anna Gagliardi Gzona Bajraktari-Sylejmani Elisabetta Barocelli Johanna Weiss Juan Pablo Rigalli |
| author_facet | Anna Gagliardi Gzona Bajraktari-Sylejmani Elisabetta Barocelli Johanna Weiss Juan Pablo Rigalli |
| author_sort | Anna Gagliardi |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T23:47:11Z |
| format | Article |
| id | doaj.art-142974420a2d45979a94afb9bea5d278 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-10T23:47:11Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-142974420a2d45979a94afb9bea5d2782023-11-19T01:55:02ZengMDPI AGLife2075-17292023-08-01138174510.3390/life13081745Extracellular Vesicles as Surrogates for Drug Metabolism and Clearance: Promise vs. RealityAnna Gagliardi0Gzona Bajraktari-Sylejmani1Elisabetta Barocelli2Johanna Weiss3Juan Pablo Rigalli4Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, GermanyDepartment of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, GermanyDepartment of Food and Drug, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, ItalyDepartment of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, GermanyDepartment of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, GermanyDrug-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.https://www.mdpi.com/2075-1729/13/8/1745ABC transportersdrug clearancedrug-metabolizing enzymesdrug transportersexosomesextracellular vesicles |
| spellingShingle | Anna Gagliardi Gzona Bajraktari-Sylejmani Elisabetta Barocelli Johanna Weiss Juan Pablo Rigalli Extracellular Vesicles as Surrogates for Drug Metabolism and Clearance: Promise vs. Reality Life ABC transporters drug clearance drug-metabolizing enzymes drug transporters exosomes extracellular vesicles |
| 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 | ABC transporters drug clearance drug-metabolizing enzymes drug transporters exosomes extracellular vesicles |
| url | https://www.mdpi.com/2075-1729/13/8/1745 |
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