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      • Record: found
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      Extracellular Vesicles as Natural, Safe and Efficient Drug Delivery Systems

      review-article
      Author(s): 1 , 1 , 2 , 1 , 2 , *
      Publication date (Electronic):
      Journal: Pharmaceutics
      Publisher: MDPI
      Keywords: extracellular vesicles, isolation methods, drug carriers

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          Abstract

          Extracellular vesicles (EVs) are particles naturally released from cells, delimited by a lipid bilayer, carrying functionally active biological molecules. In addition to their physiological role in cellular communication, the interest of the scientific community has recently turned to the use of EVs as vehicles for delivering therapeutic molecules. Several attempts are being made to ameliorate drug encapsulation and targeting, but these efforts are thwarted if the starting material does not meet stringent quality criteria. Here, we take a step back to the sources and isolation procedures that could guarantee significant improvements in the purification of EVs to be used as drug carriers, highlighting the advantages and shortcomings of each approach.

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          Using exosomes, naturally-equipped nanocarriers, for drug delivery.

          Elena Batrakova, Myung Soo Kim (2015)
          Exosomes offer distinct advantages that uniquely position them as highly effective drug carriers. Comprised of cellular membranes with multiple adhesive proteins on their surface, exosomes are known to specialize in cell-cell communications and provide an exclusive approach for the delivery of various therapeutic agents to target cells. In addition, exosomes can be amended through their parental cells to express a targeting moiety on their surface, or supplemented with desired biological activity. Development and validation of exosome-based drug delivery systems are the focus of this review. Different techniques of exosome isolation, characterization, drug loading, and applications in experimental disease models and clinic are discussed. Exosome-based drug formulations may be applied to a wide variety of disorders such as cancer, various infectious, cardiovascular, and neurodegenerative disorders. Overall, exosomes combine benefits of both synthetic nanocarriers and cell-mediated drug delivery systems while avoiding their limitations.
          Article 0 comments Cited 394 times – based on 0 reviews     Review now
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            Dynamic biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter.

            Charles P. Lai, Osama Mardini, Maria Ericsson … (2014)
            Extracellular vesicles (EVs) are nanosized vesicles released by normal and diseased cells as a novel form of intercellular communication and can serve as an effective therapeutic vehicle for genes and drugs. Yet, much remains unknown about the in vivo properties of EVs such as tissue distribution, blood levels, and urine clearance, important parameters that will define their therapeutic effectiveness and potential toxicity. Here we combined Gaussia luciferase and metabolic biotinylation to create a sensitive EV reporter (EV-GlucB) for multimodal imaging in vivo, as well as monitoring of EV levels in the organs and biofluids ex vivo after administration of EVs. Bioluminescence and fluorescence-mediated tomography imaging on mice displayed a predominant localization of intravenously administered EVs in the spleen followed by the liver. Monitoring EV signal in the organs, blood, and urine further revealed that the EVs first undergo a rapid distribution phase followed by a longer elimination phase via hepatic and renal routes within six hours, which are both faster than previously reported using dye-labeled EVs. Moreover, we demonstrate systemically injected EVs can be delivered to tumor sites within an hour following injection. Altogether, we show the EVs are dynamically processed in vivo with accurate spatiotemporal resolution and target a number of normal organs as well as tumors with implications for disease pathology and therapeutic design.
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              Ultrafiltration with size-exclusion liquid chromatography for high yield isolation of extracellular vesicles preserving intact biophysical and functional properties.

              Joel Nordin, Jia Lee, Pieter Vader … (2015)
              Extracellular vesicles (EVs) are natural nanoparticles that mediate intercellular transfer of RNA and proteins and are of great medical interest; serving as novel biomarkers and potential therapeutic agents. However, there is little consensus on the most appropriate method to isolate high-yield and high-purity EVs from various biological fluids. Here, we describe a systematic comparison between two protocols for EV purification: ultrafiltration with subsequent liquid chromatography (UF-LC) and differential ultracentrifugation (UC). A significantly higher EV yield resulted from UF-LC as compared to UC, without affecting vesicle protein composition. Importantly, we provide novel evidence that, in contrast to UC-purified EVs, the biophysical properties of UF-LC-purified EVs are preserved, leading to a different in vivo biodistribution, with less accumulation in lungs. Finally, we show that UF-LC is scalable and adaptable for EV isolation from complex media types such as stem cell media, which is of huge significance for future clinical applications involving EVs.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Pharmaceutics
                Journal ID (iso-abbrev): Pharmaceutics
                Journal ID (publisher-id): pharmaceutics
                Title: Pharmaceutics
                Publisher: MDPI
                ISSN (Electronic): 1999-4923
                Publication date (Electronic): 28 October 2019
                Publication date Collection: November 2019
                Volume: 11
                Issue: 11
                Electronic Location Identifier: 557
                Affiliations
                [1 ]U.O. Cellular Oncology, Ospedale Policlinico San Martino, 16132 Genova, Italy; vilfed@ 123456libero.it (F.V.); rodolfo.quarto@ 123456unige.it (R.Q.)
                [2 ]Department of Experimental Medicine, University of Genova, 16132 Genova, Italy
                Author notes
                [* ]Correspondence: roberta.tasso@ 123456unige.it ; Tel.: +39-010-555-8394
                Article
                Publisher ID: pharmaceutics-11-00557
                DOI: 10.3390/pharmaceutics11110557
                PMC ID: 6920944
                PubMed ID: 31661862
                SO-VID: 7fb27459-b018-4c1a-8571-e22f4a8ba30f
                Copyright © © 2019 by the authors.
                License:

                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 ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 28 August 2019
                Date accepted : 14 October 2019
                Categories
                Subject: Review

                Keywords: extracellular vesicles,isolation methods,drug carriers
                Data availability:
                Keywords: extracellular vesicles, isolation methods, drug carriers

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