Extracellular vesicles as the next-generation modulators of pharmacokinetics and pharmacodynamics of medications and their potential as adjuvant therapeutics

Jiaqi Liu , Joel Z. Nordin , Andrew J. McLachlan , Wojciech Chrzanowski

Clinical and Translational Medicine ›› 2024, Vol. 14 ›› Issue (8) : e70002

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Clinical and Translational Medicine ›› 2024, Vol. 14 ›› Issue (8) : e70002 DOI: 10.1002/ctm2.70002
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Extracellular vesicles as the next-generation modulators of pharmacokinetics and pharmacodynamics of medications and their potential as adjuvant therapeutics

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Abstract

•Existing solutions for pharmacokinetics and pharmacodynamics modulation are limited.

•Extracellular vesicles can optimise pharmacokinetics as a drug delivery vehicle.

•Biogenesis and administration of extracellular vesicles can signal cell response.

•The pharmaceutical potential of extracellular vesicles can be enhanced by surface and cargo bioengineering.

•When using extracellular vesicles as modulators of pharmacokinetics and pharmacodynamics, the ‘context of use’ must be considered.

Keywords

context of use / emerging therapeutics / extracellular vesicle / nanomedicine / pharmacodynamics / pharmacokinetics / pharmacological modulation

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Jiaqi Liu, Joel Z. Nordin, Andrew J. McLachlan, Wojciech Chrzanowski. Extracellular vesicles as the next-generation modulators of pharmacokinetics and pharmacodynamics of medications and their potential as adjuvant therapeutics. Clinical and Translational Medicine, 2024, 14(8): e70002 DOI:10.1002/ctm2.70002

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References

[1]

QuallsKE. Pharmacokinetics and pharmacodynamics. Neurochemistry in Clinical Practice. Springer International Publishing; 2022:313-316.

[2]

ByersJP, SarverJG. Pharmacokinetic modeling. Pharmacology. Elsevier; 2009:201-277.

[3]

ZaborowskiMP, BalajL, BreakefieldXO, LaiCP. Extracellular vesicles: composition, biological relevance, and methods of study. Bioscience. 2015;65(8):783-797.

[4]

Yáñez-MóM, SiljanderPRM, AndreuZ, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4(1):27066.

[5]

TkachM, Théry C. Communication by extracellular vesicles: where we are and where we need to go. Cell. 2016;164(6):1226-1232.

[6]

TettaC, GhigoE, SilengoL, Deregibus MC, CamussiG. Extracellular vesicles as an emerging mechanism of cell-to-cell communication. Endocrine. 2013;44(1):11-19.

[7]

FuscoC, De Rosa G, SpatoccoI, et al. Extracellular vesicles as human therapeutics: a scoping review of the literature. J Extracell Vesicles. 2024;13(5):e12433.

[8]

KlyachkoNL, ArztCJ, LiSM, Gololobova OA, BatrakovaEV. Extracellular vesicle-based therapeutics: preclinical and clinical investigations. Pharmaceutics. 2020;12(12):1171.

[9]

XieJ, LiQ, NieS. Bacterial extracellular vesicles: an emerging postbiotic. Trends Food Sci Technol. 2024;143:104275.

[10]

UrzìO, Raimondo S, AlessandroR. Extracellular vesicles from plants: current knowledge and open questions. Int J Mol Sci. 2021;22(10):5366.

[11]

WangL, YuX, ZhouJ, Su C. Extracellular vesicles for drug delivery in cancer treatment. Biol Proced Online. 2023;25(1):28.

[12]

O’NeillCP, Gilligan KE, DwyerRM. Role of extracellular vesicles (EVs) in cell stress response and resistance to cancer therapy. Cancers (Basel). 2019;11(2):136.

[13]

HanJ, KimS, HwangYH, et al. Novel personalized cancer vaccine using tumor extracellular vesicles with attenuated tumorigenicity and enhanced immunogenicity. Adv Sci (Weinh). 2024;11(25):e2308662.

[14]

VaderP, MolEA, PasterkampG, Schiffelers RM. Extracellular vesicles for drug delivery. Adv Drug Deliv Rev. 2016;106:148-156.

[15]

DownesKJ, HahnA, WilesJ, Courter JD, VinksAA. Dose optimisation of antibiotics in children: application of pharmacokinetics/pharmacodynamics in paediatrics. Int J Antimicrob Agents. 2014;43(3):223-230.

[16]

BazzanE, Tinè M, CasaraA, et al. Critical review of the evolution of extracellular vesicles’ knowledge: from 1946 to today. Int J Mol Sci. 2021;22(12):6417.

[17]

Fda.gov. Accessed August 20, 2023. http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/AbbreviatedNewDrugApplicationANDAGenerics/UCM292676.pdf

[18]

HabetS. Narrow therapeutic index drugs: clinical pharmacology perspective. J Pharm Pharmacol. 2021;11(10):1285-1291.

[19]

PalleriaC, Di Paolo A, GiofrèC, et al. Pharmacokinetic drug-interaction and their implication in clinical management. J Res Med Sci. 2013;18(7):601-610.

[20]

DanesiR, Innocenti F, FogliS. Pharmacokinetics and pharmacodynamics of combination chemotherapy with paclitaxel and epirubicin in breast cancer patients: epirubicin-paclitaxel interaction in cancer patients. Br J Clin Pharmacol. 2002;13(13):508-518.

[21]

AhadA, AkhtarN, GuptaDK, et al. Ethosomes: a potential vesicular carrier for drug delivery. Systems of Nanovesicular Drug Delivery. Elsevier; 2022:221-237.

[22]

MorganDJ, McleanAJ. Clinical pharmacokinetic and pharmacodynamic considerations in patients with liver disease: an update. Clin Pharmacokinet. 1995;55(5):370-391.

[23]

CorsonelloA, PedoneC, IncalziR. Age-related pharmacokinetic and pharmacodynamic changes and related risk of adverse drug reactions. Curr Med Chem. 2010;17(6):571-584.

[24]

O’HaraK. Paediatric pharmacokinetics and drug doses. Aust Prescr. 2016;39(6):208-210.

[25]

GanSH, IsmailR, Wan AdnanWA, Zulmi W. Impact of CYP2D6 genetic polymorphism on tramadol pharmacokinetics and pharmacodynamics. Mol Diagn Ther. 2007;11(3):171-181.

[26]

TakuathungN, Sakuludomkan M, KoonrungsesomboonW. The impact of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of mycophenolic acid: systematic review and meta-analysis. Clin Pharmacokinet. 2021;20(20):1291-1302.

[27]

ZhangHJ, ZhangXH, LiuJ, et al. Effects of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of proton pump inhibitors. Pharmacol Res. 2020;152:104606.

[28]

GuptaD, Zickler AM, El AndaloussiS. Dosing extracellular vesicles. Adv Drug Deliv Rev. 2021;178:113961.

[29]

WiklanderOPB, NordinJZ, O’LoughlinA, et al. Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting. J Extracell Vesicles. 2015;4(1):26316.

[30]

JurgielewiczBJ, YaoY, SticeSL. Kinetics and specificity of HEK293T extracellular vesicle uptake using imaging flow cytometry. Nanoscale Res Lett. 2020;15(1):170. http://creativecommons.org/licenses/by/4.0/.

[31]

BuschmannD, Mussack V, ByrdJB. Separation, characterization, and standardization of extracellular vesicles for drug delivery applications. Adv Drug Deliv Rev. 2021;174:348-368.

[32]

LiangX, NiuZ, GalliV, et al. Extracellular vesicles engineered to bind albumin demonstrate extended circulation time and lymph node accumulation in mouse models. J Extracell Vesicles. 2022;11(7):e12248.

[33]

TangTT, WangB, LvLL, LiuBC. Extracellular vesicle-based nanotherapeutics: emerging frontiers in anti-inflammatory therapy. Theranostics. 2020;10(18):8111-8129.

[34]

MehryabF, Taghizadeh F, GoshtasbiN, MeratiF, Rabbani S, HaeriA. Exosomes as cutting-edge therapeutics in various biomedical applications: an update on engineering, delivery, and preclinical studies. Biochimie. 2023;213:139-167.

[35]

XuM, FengT, LiuB, et al. Engineered exosomes: desirable target-tracking characteristics for cerebrovascular and neurodegenerative disease therapies. Theranostics. 2021;11(18):8926-8944.

[36]

Hernández-DíazcouderA, Díaz-GodínezC, CarreroJC. Extracellular vesicles in COVID-19 prognosis, treatment, and vaccination: an update. Appl Microbiol Biotechnol. 2023;107(7-8):2131-2141.

[37]

ZhaoR, WangL, WangT, Xian P, WangH, LongQ. Inhalation of MSC-EVs is a noninvasive strategy for ameliorating acute lung injury. J Control Release. 2022;345:214-230.

[38]

YerneniSS, Yalcintas EP, SmithJD, AverickS, Campbell PG, OzdoganlarOB. Skin-targeted delivery of extracellular vesicle-encapsulated curcumin using dissolvable microneedle arrays. Acta Biomater. 2022;149:198-212.

[39]

ChanpimolS, SeamonB, HernandezH, Harris-Love M, BlackmanMR. Using Xbox kinect motion capture technology to improve clinical rehabilitation outcomes for balance and cardiovascular health in an individual with chronic TBI. Arch Physiother. 2017;7(1):6.

[40]

MathieuM, Martin-Jaular L, LavieuG, ThéryC. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol. 2019;21(1):9-17.

[41]

VarkouhiAK, Scholte M, StormG, HaismaHJ. Endosomal escape pathways for delivery of biologicals. J Control Release. 2011;151(3):220-228.

[42]

NiuG, JianT, GaiY, ChenJ. Microbiota and plant-derived vesicles that serve as therapeutic agents and delivery carriers to regulate metabolic syndrome. Adv Drug Deliv Rev. 2023;196:114774.

[43]

PaternaA, RaoE, AdamoG, et al. Isolation of extracellular vesicles from microalgae: a renewable and scalable bioprocess. Front Bioeng Biotechnol. 2022;10:836747.

[44]

KameliN, Dragojlovic-Kerkache A, SavelkoulP, StassenFR. Plant-derived extracellular vesicles: current findings, challenges, and future applications. Membranes (Basel). 2021;11(6):411.

[45]

BryantWA, StentzR, Le GallG, Sternberg MJE, CardingSR, WilhelmT. In silico analysis of the small molecule content of outer membrane vesicles produced by Bacteroides thetaiotaomicron indicates an extensive metabolic link between microbe and host. Front Microbiol. 2017;8:2440.

[46]

RaposoG, StahlPD. Extracellular vesicles: a new communication paradigm? Nat Rev Mol Cell Biol. 2019;20(9):509-510.

[47]

StauferO, Hernandez Bücher JE, FichtlerJ, SchröterM, Platzman I, SpatzJP. Vesicle induced receptor sequestration: mechanisms behind extracellular vesicle-based protein signaling. Adv Sci (Weinh). 2022;9(13):e2200201.

[48]

PittJM, Kroemer G, ZitvogelL. Extracellular vesicles: masters of intercellular communication and potential clinical interventions. J Clin Invest. 2016;126(4):1139-1143.

[49]

CesselliD, Parisse P, AleksovaA, et al. Extracellular vesicles: how drug and pathology interfere with their biogenesis and function. Front Physiol. 2018;9:1394.

[50]

SavinaA, Furlán M, VidalM, ColomboMI. Exosome release is regulated by a calcium-dependent mechanism in K562 cells. J Biol Chem. 2003;278(22):20083-20090.

[51]

XiaoX, XiaoF, ZhaoM, et al. Treating normal early gestation placentae with preeclamptic sera produces extracellular micro and nano vesicles that activate endothelial cells. J Reprod Immunol. 2017;120:34-41.

[52]

YatesAG, PinkRC, ErdbrüggerU, et al. In sickness and in health: the functional role of extracellular vesicles in physiology and pathology in vivo: part I: health and normal physiology. J Extracell Vesicles. 2022;11(1):e12151.

[53]

PalominoÑ, Vanpouille RA, CostantiniC, MargolisPE. Microbiota-host communications: bacterial extracellular vesicles as a common language. PLoS Pathog. 2021;37(5):e1009508.

[54]

López de Las HazasMC, Tomé-CarneiroJ, Del Pozo-Aceb. L, et al. Therapeutic potential of plant-derived extracellular vesicles as nanocarriers for exogenous miRNAs. Pharmacol Res. 2023;198:106999.

[55]

Rankin-TurnerS, VaderP, O’DriscollL, GiebelB, HeaneyLM, DaviesOG. A call for the standardised reporting of factors affecting the exogenous loading of extracellular vesicles with therapeutic cargos. Adv Drug Deliv Rev. 2021;173:479-491.

[56]

KimHI, ParkJ, ZhuY, WangX, HanY, ZhangD. Recent advances in extracellular vesicles for therapeutic cargo delivery. Exp Mol Med. 2024;56(4):836-849.

[57]

JamurMC, OliverC. Permeabilization of cell membranes. Immunocytochemical Methods and Protocols. Humana Press; 2010:63-66.

[58]

HerrmannIK, WoodMJA, FuhrmannG. Extracellular vesicles as a next-generation drug delivery platform. Nat Nanotechnol. 2021;16(7):748-759.

[59]

ElsharkasyOM, Hegeman CV, LansweersI, et al. A modular strategy for extracellular vesicle-mediated CRISPR-Cas9 delivery through aptamer-based loading and UV-activated cargo release. bioRxiv. 2024.

[60]

van der KoogL, GandekTB, NagelkerkeA. Liposomes and extracellular vesicles as drug delivery systems: a comparison of composition, pharmacokinetics, and functionalization. Adv Healthc Mater. 2022;11(5):e2100639.

[61]

MoholkarDN, Kandimalla R, GuptaRC, AqilF. Advances in lipid-based carriers for cancer therapeutics: liposomes, exosomes and hybrid exosomes. Cancer Lett. 2023;565:216220.

[62]

Toro-CórdovaA, Ledezma-Gallegos F, Mondragon-FuentesL, et al. Determination of liposomal cisplatin by high-performance liquid chromatography and its application in pharmacokinetic studies. J Chromatogr Sci. 2016;54(6):1016-1021.

[63]

CaronWP, Clewell H, DedrickR, et al. Allometric scaling of pegylated liposomal anticancer drugs. J Pharmacokinet Pharmacodyn. 2011;38(5):653-669.

[64]

Alvarez-ErvitiL, SeowY, YinH, BettsC, LakhalS, Wood MJA. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011;29(4):341-345.

[65]

PippaLF, de Oliveira ML, RochaA, de AndradeJM, Lanchote VL. Total, renal and hepatic clearances of doxorubicin and formation clearance of doxorubicinol in patients with breast cancer: estimation of doxorubicin hepatic extraction ratio. J Pharm Biomed Anal. 2020;185:113231.

[66]

ZhuangX, XiangX, GrizzleW, et al. Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther. 2011;19(10):1769-1779.

[67]

van NielG, D’Angelo G, RaposoG. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018;19(4):213-228.

[68]

HoshinoA, Costa-Silva B, ShenTL, et al. Tumour exosome integrins determine organotropic metastasis. Nature. 2015;527(7578):329-335.

[69]

MurphyDE, de Jong OG, BrouwerM, et al. Extracellular vesicle-based therapeutics: natural versus engineered targeting and trafficking. Exp Mol Med. 2019;51(3):1-12.

[70]

ShimodaA, TaharaY, SawadaSI, Sasaki Y, AkiyoshiK. Glycan profiling analysis using evanescent-field fluorescence-assisted lectin array: importance of sugar recognition for cellular uptake of exosomes from mesenchymal stem cells. Biochem Biophys Res Commun. 2017;491(3):701-707.

[71]

MatsumotoA, Takahashi Y, NishikawaM, et al. Role of phosphatidylserine-derived negative surface charges in the recognition and uptake of intravenously injected B16BL6-derived exosomes by macrophages. J Pharm Sci. 2017;106(1):168-175.

[72]

JiaG, HanY, AnY, et al. NRP-1 targeted and cargo-loaded exosomes facilitate simultaneous imaging and therapy of glioma in vitro and in vivo. Biomaterials. 2018;178:302-316.

[73]

ValadiH, Ekström K, BossiosA, SjöstrandM, LeeJJ, LötvallJO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654-659.

[74]

OhnoSI, Takanashi M, SudoK, et al. Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol Ther. 2013;21(1):185-191.

[75]

KooijmansSAA, Fliervoet LAL, van der MeelR, et al. PEGylated and targeted extracellular vesicles display enhanced cell specificity and circulation time. J Control Release. 2016;224:77-85.

[76]

Conde-VancellsJ, Gonzalez E, LuSC, MatoJM, Falcon-Perez JM. Overview of extracellular microvesicles in drug metabolism. Expert Opin Drug Metab Toxicol. 2010;6(5):543-554.

[77]

RowlandA, Ruanglertboon W, van DykM, et al. Plasma extracellular nanovesicle (exosome)-derived biomarkers for drug metabolism pathways: a novel approach to characterize variability in drug exposure: exosome-derived markers of drug exposure. Br J Clin Pharmacol. 2019;85(1):216-226.

[78]

KumarS, SinhaN, GerthKA, Rahman MA, YallapuMM, MiddeNM. Specific packaging and circulation of cytochromes P450, especially 2E1 isozyme, in human plasma exosomes and their implications in cellular communications. Biochem Biophys Res Commun. 2017;491(3):675-680.

[79]

GagliardiA, Bajraktari-Sylejmani G, BarocelliE, WeissJ, Rigalli JP. Extracellular vesicles as surrogates for drug metabolism and clearance: promise vs. reality. Life (Basel). 2023;13(8):1745.

[80]

UseckaiteZ, Rodrigues AD, HopkinsAM, et al. Role of extracellular vesicle-derived biomarkers in drug metabolism and disposition. Drug Metab Dispos. 2021;49(11):961-971.

[81]

GuptaD, Wiklander OPB, GörgensA, et al. Amelioration of systemic inflammation via the display of two different decoy protein receptors on extracellular vesicles. Nat Biomed Eng. 2021;5(9):1084-1098.

[82]

LugowskaI, Teterycz P, RutkowskiP. Immunotherapy of melanoma. Contemp Oncol (Pozn). 2018;2018(1):61-67.

[83]

RobbinsPD, Morelli AE. Regulation of immune responses by extracellular vesicles. Nat Rev Immunol. 2014;14(3):195-208.

[84]

BaqueroDP, BorrelG, GaziA, et al. Biogenesis of DNA-carrying extracellular vesicles by the dominant human gut methanogenic archaeon. bioRxiv. 2024.

[85]

NémethK, VargaZ, LenzingerD, et al. Extracellular vesicle release and uptake by the liver under normo-and hyperlipidemia. Cell Mol Life Sci. 2021;78(23):7589-7604.

[86]

WiklanderOPB, MamandDR, MohammadDK, et al. Antibody-displaying extracellular vesicles for targeted cancer therapy. Nat Biomed Eng. 2024: 1-16.

[87]

DanilushkinaAA, EmeneCC, BarlevNA, Gomzikova MO. Strategies for engineering of extracellular vesicles. Int J Mol Sci. 2023;24(17):13247.

[88]

LevyD, Jeyaram A, BornLJ, et al. Impact of storage conditions and duration on function of native and cargo-loaded mesenchymal stromal cell extracellular vesicles. Cytotherapy. 2023;25(5):502-509.

[89]

GörgensA, CorsoG, HageyDW, et al. Identification of storage conditions stabilizing extracellular vesicles preparations. J Extracell Vesicles. 2022;11(6):e12238.

[90]

Kawai-HaradaY, El Itawi H, KomuroH, HaradaM. Evaluation of EV storage buffer for efficient preservation of engineered extracellular vesicles. Int J Mol Sci. 2023;24(16):12841.

[91]

WelshJA, Goberdhan DCI, O’DriscollL, et al. Minimal information for studies of extracellular vesicles (MISEV2023):from basic to advanced approaches. J Extracell Vesicles. 2024;13(2):e12404.

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2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.

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