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Gupta et al. Extracell Vesicles Circ Nucleic Acids 2023;4:170-90  Extracellular Vesicles and
               DOI: 10.20517/evcna.2023.12
                                                                        Circulating Nucleic Acids




               Review                                                                        Open Access



               Biodistribution of therapeutic extracellular vesicles


                                               2
                          1,2
                                                                1
               Dhanu Gupta , Oscar P.B Wiklander , Matthew J.A Wood , Samir El-Andaloussi 2
               1
                Department of Paediatrics. University of Oxford, Oxford OX3 7TY, UK.
               2
                Biomolecular Medicine, Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska
               Institutet, Huddinge 14151, Sweden.
               Correspondence to: Dr. Dhanu Gupta, Department of Paediatrics, University of Oxford, Campus, Old Rd, Roosevelt Dr,
               Headington, Oxford OX3 7TY, UK. E-mail: Dhanu.gupta@paediatrics.ox.ac.uk
               How to cite this article: Gupta D, Wiklander OPB, Wood MJA, El-Andaloussi S. Biodistribution of therapeutic extracellular
               vesicles. Extracell Vesicles Circ Nucleic Acids 2023;4:170-90. https://dx.doi.org/10.20517/evcna.2023.12

               Received: 7 Feb 2023  First Decision: 7 Mar 2023  Revised: 27 Mar 2023  Accepted: 3 Apr 2023  Published: 19 Apr 2023

               Academic Editor: Yoke Peng Loh  Copy Editor: Ying Han  Production Editor: Ying Han

               Abstract
               The field of extracellular vesicles (EVs) has seen a tremendous paradigm shift in the past two decades, from being
               regarded as cellular waste bags to being considered essential mediators in intercellular communication. Their
               unique ability to transfer macromolecules across cells and biological barriers has made them a rising star in drug
               delivery. Mounting evidence suggests that EVs can be explored as efficient drug delivery vehicles for a range of
               therapeutic macromolecules. In contrast to many synthetic delivery systems, these vesicles appear exceptionally
               well tolerated in vivo. This tremendous development in the therapeutic application of EVs has been made through
               technological advancement in labelling and understanding the in vivo biodistribution of EVs. Here in this review, we
               have summarised the recent findings in EV in vivo pharmacokinetics and discussed various biological barriers that
               need to be surpassed to achieve tissue-specific delivery.

               Keywords: Exosomes, in vivo biodistribution, extracellular vesicles, targeted delivery, CNS targeting



               INTRODUCTION
               Extracellular vesicles (EVs) are a heterogeneous group of membranous nanoparticles actively secreted by all
               cells. Based on their biogenesis, EVs are differentiated into three main subtypes: microvesicles (MVs),
                                          [1,2]
               exosomes, and apoptotic bodies . In addition to this classification, it is becoming increasingly evident that
               various sub-populations of vesicles exist, especially different types of exosomes . EVs contain biologically
                                                                                   [3]





                           © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
                           International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
                           adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
               long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
               indicate if changes were made.

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