Visualization of exogenous delivery of nanoformulated butyrylcholinesterase to the central nervous system

Andrea Gaydess, Ellen Duysen, Yuan Li, Vladimir Gilman, Alexander Kabanov, Oksana Lockridge, Tatiana Bronich

Research output: Contribution to journalArticle

27 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)295-298
Number of pages4
JournalChemico-Biological Interactions
Volume187
Issue number1-3
DOIs
StatePublished - Sep 2010

Keywords

  • Block ionomer complexes
  • Butyrylcholinesterase
  • CNS drug delivery
  • Nanotechnology

ASJC Scopus subject areas

  • Toxicology

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