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Here, we report that SynB1\u2010ELP\u2010p50i, a novel protein inhibitor of the nuclear factor kappa B (NF\u2010\u03baB) inflammatory cascade bound to the drug carrier elastin\u2010like polypeptide (ELP), decreases NF\u2010\u03baB induced inflammatory cytokine production in cultured macrophages, crosses the plasma membrane and accumulates in the cytoplasm of both neurons and microglia in vitro, and accumulates at the infarct site where the blood\u2013brain barrier (BBB) is compromised following middle cerebral artery occlusion (MCAO) in rats. Additionally, SynB1\u2010ELP\u2010p50i treatment reduces infarct volume by 11.86% compared to saline\u2010treated controls 24\u2009h following MCAO. Longitudinally, SynB1\u2010ELP\u2010p50i treatment improves survival for 14\u2009days following stroke with no effects of toxicity or peripheral organ dysfunction. These results show high potential for ELP\u2010delivered biologics for therapy of ischemic stroke and other central nervous system disorders and further support targeting inflammation in ischemic stroke.<\/jats:p>","DOI":"10.1096\/fj.202300309rr","type":"journal-article","created":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T11:09:19Z","timestamp":1688468959000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Elastin\u2010like polypeptide delivery of anti\u2010inflammatory peptides to the brain following ischemic stroke"],"prefix":"10.1096","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9875-6022","authenticated-orcid":false,"given":"John Aaron","family":"Howell","sequence":"first","affiliation":[{"name":"Graduate Program in Neuroscience University of Mississippi Medical Center  Jackson Mississippi USA"},{"name":"Department of Neurology University of Mississippi Medical Center  Jackson 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