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Their stability, natural structure, composition, and bioavailability make them good candidates as drug vehicles. Here, EVs were isolated from amniotic fluid (AF) through differential centrifugation, and characterized for size (&lt;200\u2009nm), structure, and composition, their effectiveness on the human PC12 cell line, and brain of chick embryos exposed to sodium valproate (animal autistic model). Sulforaphane (SFN) was employed as a bioactive compound and then encapsulated into Evs using three methods including passive (incubation), active (sonication), and active\u2010passive (sonication\u2010incubation). Further, the loading and in vitro releases of SFN fitted the Korsmeyer\u2013Peppas (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u20090.99) kinetic model by non\u2010Fickian diffusion case II (<jats:italic>n<\/jats:italic>\u00a0=\u00a00.44, passive loading) and Fickian diffusion case I (<jats:italic>n<\/jats:italic>\u00a0=\u00a00.41, active and active\u2010passive loading). SFN\u2010loaded EVs (SFN@EVs; 11\u2009\u03bcM: 103\u2009nM) stimulated hPC\u201012 cell proliferation. The gene expression analysis revealed that SFN@EVs could upregulate Nrf2 and reduce IL\u20106 expression. Eventually, histopathological results of the coronal cross\u2010section of the chick embryos brain showed treatment with SFN@EVs. This treatment illustrated normality in the gray and white matter and the orientation of the bipolar neurons. Our findings showed EVs' potentially acting as a gene expression regulator in autism spectrum disorder.<\/jats:p>","DOI":"10.1002\/jbm.b.35117","type":"journal-article","created":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T14:34:53Z","timestamp":1656945293000},"page":"2636-2648","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Sustained release of sulforaphane by bioactive extracellular vesicles for neuroprotective effect on chick model"],"prefix":"10.1002","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1523-4876","authenticated-orcid":false,"given":"Mona","family":"Shahlaei","sequence":"first","affiliation":[{"name":"Department of Nanotechnology and Advanced Materials Materials and Energy Research Centre  Karaj 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