title: Visualization of exogenous delivery of nanoformulated butyrylcholinesterase to the central nervous system.
abstract: Butyrylcholinesterase (BChE) is an efficient bioscavenger of highly toxic organophosphorus poisons and nerve agents. However, BChE administered into the periphery does not provide significant protection of the central nervous system (CNS) due to rejection by the blood-brain barrier. In this study, we evaluated the feasibility of delivering BChE to the CNS by packing it into a block ionomer complex of nanoscale size with a cationic poly(l-lysine)-graft-poly(ethylene oxide) (PLL-g-PEO) copolymer. The multimolecular structure of BChE/PLL-g-PEO complexes was further reinforced by formation of cross-links between the polymer chains. The resulting cross-linked complexes were stable against dilution without significant loss of BChE enzymatic activity. In some cases the BChE was labeled with fluorescent IRDye 800CW before it was incorporated into nanoparticles. BChE/PLL-g-PEO complexes were injected into mice intramuscularly and intravenously. In vivo imaging showed incorporation of the fluorescently labeled BChE in brain. Activity assays showed that BChE remained active in the brain at 72-h post-injection. It was concluded that nanocomplexes can deliver the 340 kDa BChE tetramer to the brain.
authors.affiliation: College of Pharmacy and Center for Drug Delivery and Nanomedicine, University of Nebraska Medical Center, Omaha, NE 68198-5830, United States.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gaydess
authors.forename: Ellen
authors.initials: E
authors.lastname: Duysen
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Vladimir
authors.initials: V
authors.lastname: Gilman
authors.forename: Alexander
authors.initials: A
authors.lastname: Kabanov
authors.forename: Oksana
authors.initials: O
authors.lastname: Lockridge
authors.forename: Tatiana
authors.initials: T
authors.lastname: Bronich
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry* / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D006801:Humans; D051379:Mice; D057054:Molecular Imaging; D053758:Nanoparticles / Q000737:chemistry; D049329:Nanostructures / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011107:Polylysine / Q000737:chemistry; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D014867:Water; D011107:Polylysine; D011092:Polyethylene Glycols; D002265:Carboxylic Ester Hydrolases; C021487:butyrylesterase