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 K Bronich

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 1 2010

Fingerprint

Butyrylcholinesterase
Neurology
Visualization
Central Nervous System
Polyethylene oxides
Phase locked loops
Brain
Poisons
Ethylene Oxide
Ionomers
Blood-Brain Barrier
Grafts
Nanoparticles
Dilution
Lysine
Assays
Polymers
Copolymers
Transplants

Keywords

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

ASJC Scopus subject areas

  • Toxicology

Cite this

Visualization of exogenous delivery of nanoformulated butyrylcholinesterase to the central nervous system. / Gaydess, Andrea; Duysen, Ellen; Li, Yuan; Gilman, Vladimir; Kabanov, Alexander; Lockridge, Oksana; Bronich, Tatiana K.

In: Chemico-Biological Interactions, Vol. 187, No. 1-3, 01.09.2010, p. 295-298.

Research output: Contribution to journalArticle

Gaydess, Andrea ; Duysen, Ellen ; Li, Yuan ; Gilman, Vladimir ; Kabanov, Alexander ; Lockridge, Oksana ; Bronich, Tatiana K. / Visualization of exogenous delivery of nanoformulated butyrylcholinesterase to the central nervous system. In: Chemico-Biological Interactions. 2010 ; Vol. 187, No. 1-3. pp. 295-298.
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