title: Exosomes as drug delivery vehicles for Parkinson's disease therapy.
abstract: Exosomes are naturally occurring nanosized vesicles that have attracted considerable attention as drug delivery vehicles in the past few years. Exosomes are comprised of natural lipid bilayers with the abundance of adhesive proteins that readily interact with cellular membranes. We posit that exosomes secreted by monocytes and macrophages can provide an unprecedented opportunity to avoid entrapment in mononuclear phagocytes (as a part of the host immune system), and at the same time enhance delivery of incorporated drugs to target cells ultimately increasing drug therapeutic efficacy. In light of this, we developed a new exosomal-based delivery system for a potent antioxidant, catalase, to treat Parkinson's disease (PD). Catalase was loaded into exosomes ex vivo using different methods: the incubation at room temperature, permeabilization with saponin, freeze-thaw cycles, sonication, or extrusion. The size of the obtained catalase-loaded exosomes (exoCAT) was in the range of 100-200nm. A reformation of exosomes upon sonication and extrusion, or permeabilization with saponin resulted in high loading efficiency, sustained release, and catalase preservation against proteases degradation. Exosomes were readily taken up by neuronal cells in vitro. A considerable amount of exosomes was detected in PD mouse brain following intranasal administration. ExoCAT provided significant neuroprotective effects in in vitro and in vivo models of PD. Overall, exosome-based catalase formulations have a potential to be a versatile strategy to treat inflammatory and neurodegenerative disorders.
authors.affiliation: Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Haney
authors.affiliation: Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Deparment of Chemical Enzymology, Faculty of Chemistry, M.V. Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Natalia L
authors.initials: NL
authors.lastname: Klyachko
authors.affiliation: Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Richa
authors.initials: R
authors.lastname: Gupta
authors.affiliation: Deparment of Chemical Enzymology, Faculty of Chemistry, M.V. Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Evgeniya G
authors.initials: EG
authors.lastname: Plotnikova
authors.affiliation: Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: He
authors.affiliation: Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Tejash
authors.initials: T
authors.lastname: Patel
authors.affiliation: Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Piroyan
authors.affiliation: Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Sokolsky
authors.affiliation: Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Deparment of Chemical Enzymology, Faculty of Chemistry, M.V. Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kabanov
authors.affiliation: Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: batrakov@email.unc.edu.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Batrakova
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D000975:Antioxidants / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002374:Catalase / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D004337:Drug Carriers; D055354:Exosomes; D005260:Female; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D050997:Nanomedicine; D053758:Nanoparticles; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine; D016716:PC12 Cells; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D000067996:RAW 264.7 Cells; D051381:Rats; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D000978:Antiparkinson Agents; D004337:Drug Carriers; D018696:Neuroprotective Agents; D016627:Oxidopamine; D002374:Catalase
keywords: Blood–brain barrier; Catalase; Exosomes; Neuroinflammation; Oxidative stress; Parkinson's disease
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