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Nanoparticle-induced enhancement of cholinesterase activity in the presence of malathion: A potential nerve agent therapeutic.

Authors :
Cowen, Todd
Bedwell, Thomas S.
Piletska, Elena V.
Rice, Helen
Piletsky, Sergey A.
Source :
International Journal of Pharmaceutics. Dec2022, Vol. 629, pN.PAG-N.PAG. 1p.
Publication Year :
2022

Abstract

[Display omitted] Organophosphate nerve agents are associated with assassination, terrorism and chemical warfare, but there has been slow progress in developing a broad-spectrum response to poisoning. For some nerve agents the oxime component of the therapy may not be effective, limiting the effectiveness of emergency treatment that is desperately needed. An alternative therapy may be possible based on accelerating enzyme (acetylcholinesterase) catalysis in unaffected adjacent enzymes. Herein we demonstrate a restoration of acetylcholinesterase activity in malathion-inhibited cell membrane preparations by the administration of functional nanoparticles. The molecularly imprinted polymer nanoparticles were designed to bind selectively to designated enzyme epitopes. Enzyme activity of membrane-bound acetylcholinesterase was measured in the presence of the organophosphate malathion and the selected nanoparticles. Enzymatic acceleration of the cholinesterase was observed at 162 ± 17 % the rate of erythrocyte ghosts without bound nanoparticles. This may restore sufficient acetylcholine hydrolysis to mitigate the effects of poisoning, offsetting the acetylcholine accumulation resulting from enzyme inhibition. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
03785173
Volume :
629
Database :
Academic Search Index
Journal :
International Journal of Pharmaceutics
Publication Type :
Academic Journal
Accession number :
160537074
Full Text :
https://doi.org/10.1016/j.ijpharm.2022.122406