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Nanoparticle-induced enhancement of cholinesterase activity in the presence of malathion: A potential nerve agent therapeutic.
Cowen, Todd; Bedwell, Thomas S; Piletska, Elena V; Rice, Helen; Piletsky, Sergey A.
Afiliación
  • Cowen T; Department of Chemistry, University of Leicester, LE1 7RH, UK. Electronic address: todd.cowen@mail.huji.ac.il.
  • Bedwell TS; Department of Chemistry, University of Leicester, LE1 7RH, UK.
  • Piletska EV; Department of Chemistry, University of Leicester, LE1 7RH, UK.
  • Rice H; Chemical, Biological and Radiological Division, Dstl Porton Down, SP4 0JQ, UK.
  • Piletsky SA; Department of Chemistry, University of Leicester, LE1 7RH, UK.
Int J Pharm ; 629: 122406, 2022 Dec 15.
Article en En | MEDLINE | ID: mdl-36395924
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Nanopartículas / Agentes Nerviosos Idioma: En Revista: Int J Pharm Año: 2022 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Nanopartículas / Agentes Nerviosos Idioma: En Revista: Int J Pharm Año: 2022 Tipo del documento: Article Pais de publicación: Países Bajos