title: Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain.
abstract: In this study, exosomes used to encapsulate curcumin (Exo-cur) or a signal transducer and activator of transcription 3 (Stat3) inhibitor, i.e., JSI124 (Exo-JSI124) were delivered noninvasively to microglia cells via an intranasal route. The results generated from three inflammation-mediated disease models, i.e., a lipopolysaccharide (LPS)-induced brain inflammation model, experimental autoimmune encephalitis and a GL26 brain tumor model, showed that mice treated intranasally with Exo-cur or Exo-JSI124 are protected from LPS-induced brain inflammation, the progression of myelin oligodendrocyte glycoprotein (MOG) peptide induced experimental autoimmune encephalomyelitis (EAE), and had significantly delayed brain tumor growth in the GL26 tumor model. Intranasal administration of Exo-cur or Exo-JSI124 led to rapid delivery of exosome encapsulated drug to the brain that was selectively taken up by microglial cells, and subsequently induced apoptosis of microglial cells. Our results demonstrate that this strategy may provide a noninvasive and novel therapeutic approach for treating brain inflammatory-related diseases.
authors.affiliation: Louisville Veterans Administration Medical Center, Louisville, Kentucky, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhuang
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Xiang
authors.forename: William
authors.initials: W
authors.lastname: Grizzle
authors.forename: Dongmei
authors.initials: D
authors.lastname: Sun
authors.forename: Shuangqin
authors.initials: S
authors.lastname: Zhang
authors.forename: Robert C
authors.initials: RC
authors.lastname: Axtell
authors.forename: Songwen
authors.initials: S
authors.lastname: Ju
authors.forename: Jiangyao
authors.initials: J
authors.lastname: Mu
authors.forename: Lifeng
authors.initials: L
authors.lastname: Zhang
authors.forename: Lawrence
authors.initials: L
authors.lastname: Steinman
authors.forename: Donald
authors.initials: D
authors.lastname: Miller
authors.forename: Huang-Ge
authors.initials: HG
authors.lastname: Zhang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000473:pathology; D004337:Drug Carriers; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D055354:Exosomes; D006801:Humans; D051379:Mice; D017628:Microglia / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D004337:Drug Carriers