Abstract
Extracellular vesicles (EVs) are membrane-bilayered nanoparticles released by most cell types. Recently, an enormous number of studies have been published on the potential of EVs as carriers of therapeutic agents. In contrast to systems such as liposomes, EVs exhibit less immunogenicity and higher engineering potential. Here, we review the most relevant publications addressing the potential and use of EVs as a drug delivery system (DDS). The information is divided based on the key steps for designing an EV-mediated delivery strategy. We discuss possible sources and isolation methods of EVs. We address the administration routes that have been tested in vivo and the tissue distribution observed. We describe the current knowledge on EV clearance, a significant challenge towards enhancing bioavailability. Also, EV-engineering approaches are described as alternatives to improve tissue and cell-specificity. Finally, a summary of the ongoing clinical trials is performed. Although the application of EVs in the clinical practice is still at an early stage, a high number of studies in animals support their potential as DDS. Thus, better treatment options could be designed to precisely increase target specificity and therapeutic efficacy while reducing off-target effects and toxicity according to the individual requirements of each patient.
Highlights
A similar strategy was effective to direct Extracellular vesicles (EVs) carrying miR-210 to ischemic brain areas [59]. Another peptide used for the same purpose is a short sequence of the rabies virus glycoprotein (RVG), wPhhiacrmhahceautsicbs e20e2n0,e1x2,pxressed in the EV-generating cells coupled to the exosomal protein Lamp21b8.oTf h37is resulted in the generation of EVs exhibiting a higher tropism for the central nervous system [218]
While good manufacturing practices (GMPs)-grade culture media and supplements and tangential flow filtration (TFF)-mediated isolation led to the production and validation of different EV suspensions, it is yet unclear whether this constitutes a cost-effective alternative
There has been an increase in the body of evidence addressing EV secretion, biodistribution and specificity
Summary
The therapeutic efficacy of any pharmacological treatment depends on achieving an optimal drug concentration at the site of action This is strongly influenced by the absorption, distribution, metabolism and excretion of therapeutic agents. Changes in the diet and metabolism, and disease states may affect, for instance, the expression and activity of drug transporters and metabolizing enzymes and, influence the concentration of a drug at its active site and its therapeutic efficacy [1,2] In this regard, selectively surpassing the physiological mechanisms responsible for limiting drug absorption, and more importantly, those mediating drug clearance, may increase drug bioavailability. PTohtiesnptioatlenistiarleifslercetfleedcteind itnhetheimimmmenesneseeexxppaannssioionn ooff kknnoowwlleeddggee wwiitthhiinn tthhiiss ffiieelldd iinn tthhee ppaasstt yyeeaarrss,, wwiitthh hhiigghh iimmppaacctt ppaappeerrss bbeeiinngg ccoonnttiinnuuoouussllyy rreelleeaasseedd aanndd sshhoowwiinngg tthheeddiviveerrsseeppoosssisbibiliiltiiteisesofofffereerdedbybyEVEsVisnindifdfieffreenretnatnaimniaml aml omdoeldse. FFiirrsstt,, tthhee tteecchhnniiqquueess ffoorr iissoollaattiioonn aanndd ppuurriiffiiccaattiioonn ooff EEVVss wwiillll bbee pprreesseenntteedd. AAfftteerrwwaarrddss,, ddiiffffeerreenntt ssttrraatteeggiieess ttoo llooaadd EEVVss wwiitthh tthheerraappeeuuttiicc aaggeennttss wwiillll bbee ddiissccuusssseedd. FFoolllloowwiinngg,, wwee wwiillll ddeessccrriibbee ppoossssiibbllee aaddmmiinniissttrraattiioonnrroouutetessfofor rEEVV-b-absaesdedthtehrearpaypaynadnhdohwotwisstuisesuspeescpifiecciitfyiciatnydabnidoabviaoialavbaiilliatbyilciatyn cbaenebnehaenncheadn.cTedh.eTsehdesiffe edriefnfetrpenhtaspehsaosfesanofEaVn-bEaVse-bdatsheedrathpeyraapreysaurme smuamrimzeadriiznedFiignuFreig1u.re 1
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