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PMID: 21915101 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain.

Molecular therapy : the journal of the American Society of Gene Therapy ·Vol. 19 ·No. 10 ·2011-00-00 ·Pages 1769-79

Zhuang X, Xiang X, Grizzle W, Sun D, Zhang S, Axtell RC, Ju S, Mu J, Zhang L, Steinman L, Miller D, Zhang HG

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.

MeSH Terms
Administration, Intranasal Animals Anti-Inflammatory Agents/administration & dosage,therapeutic use Brain Neoplasms/pathology Drug Carriers Encephalomyelitis, Autoimmune, Experimental/drug therapy Exosomes Humans Mice Microglia/metabolism
Chemicals
Anti-Inflammatory Agents Drug Carriers
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Zhuang Xiaoying
Louisville Veterans Administration Medical Center, Louisville, Kentucky, USA.
Xiang Xiaoyu
Grizzle William
Sun Dongmei
Zhang Shuangqin
Axtell Robert C
Ju Songwen
Mu Jiangyao
Zhang Lifeng
Steinman Lawrence
Miller Donald
Zhang Huang-Ge
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Article Info
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
Abbr.
Mol Ther
ISSN
1525-0024
DOI
10.1038/mt.2011.164
Published
2011-00-00
Epub
2011-00-13
Pages
1769-79
Language
English
Region
United States
NLM ID
100890581
PMCID
PMC3188748
Subset
IM
Grants
NCI NIH HHS · R01CA137037 · United States
NCI NIH HHS · R01CA116092 · United States
NCI NIH HHS · R01 CA107181 · United States
NCI NIH HHS · R01 CA116092 · United States
NCI NIH HHS · R01 CA137037 · United States
NCCIH NIH HHS · R01AT004294 · United States
NCI NIH HHS · R01CA107181 · United States
NCCIH NIH HHS · R01 AT004294 · United States
Corrections
CommentIn
PMID: 21964306
ErratumIn
PMID: 28160630
External Links
PubMed source DOI: 10.1038/mt.2011.164 PMC Full Text View journal details
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