Nano-intercalated organophosphorus-hydrolyzing enzymes in organophosphorus antagonism

AAPS PharmSciTech. 2012 Mar;13(1):112-7. doi: 10.1208/s12249-011-9728-5. Epub 2011 Dec 9.

Abstract

A dendritic poly(2-alkyloxazoline)-based polymer was studied as a new carrier system for the organophosphorus-hydrolyzing recombinant enzymes, organophosphorus acid anhydrolase and organophosphorus hydrolase. Paraoxon (PO) and diisopropylfluorophosphate (DFP) were used as model organophosphorus compounds. Changes in plasma cholinesterase activity were monitored. The cholinesterase activity was proportional to the concentrations of DFP or PO. Plasma cholinesterase activity was higher in animals receiving enzyme and oxime before the organophosphates than in the oxime-only pretreated groups. These studies suggest that cholinesterase activity can serve as an indicator for the in vivo protection by the nano-intercalated organophosphorus acid anhydrolase or organophosphorus hydrolase against organophosphorus intoxications. These studies represent a practical application of polymeric nano-delivery systems as enzyme carriers in drug antidotal therapy.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Aryldialkylphosphatase / antagonists & inhibitors*
  • Aryldialkylphosphatase / metabolism*
  • Cholinesterase Inhibitors / administration & dosage
  • Cholinesterase Inhibitors / metabolism
  • Cholinesterase Reactivators / administration & dosage
  • Cholinesterase Reactivators / metabolism
  • Dose-Response Relationship, Drug
  • Hydrolysis
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nanotechnology / methods*
  • Organophosphorus Compounds / administration & dosage
  • Organophosphorus Compounds / metabolism
  • Paraoxon / administration & dosage
  • Paraoxon / metabolism

Substances

  • Cholinesterase Inhibitors
  • Cholinesterase Reactivators
  • Organophosphorus Compounds
  • Acetylcholinesterase
  • Aryldialkylphosphatase
  • Paraoxon