Enzyme-based intravascular defense against organophosphorus neurotoxins: Synergism of dendritic-enzyme complexes with 2-PAM and atropine

I. Petrikovics, M. E. Wales, J. C. Jaszberenyi, M. Budai, S. I. Baskin, M. Szilasi, B. A. Logue, Patricia Chapela, J. R. Wild

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Novel, enzyme-complexed, nano-delivery systems have been developed to antagonize the lethal effects of organophosphorus (OP) molecules such as diisopropylfluorophosphate and paraoxon. Polymeric nanocapsules can be used to deliver metabolizing enzymes to the circulation, often increasing the enzyme's efficacy by extending their circulatory life and, in some cases, enhancing their specific activity. The bacterial enzymes organophosphorus hydrolase (OPH) and organophosphorus anhydrolase (OPAA) were encapsulated within a nanocapsule, polyoxazoline-based dendritic polymer carrier and employed in combination with the OP antagonists pralidoxime (2-PAM) and atropine. The effective doses for OPH and OPAA, respectively, were 500-550 and 1500-1650 units/kg mice; the size of the entire complex is approximately 200 nm in diameter. These studies compare the efficacy of the two enzymes as prophylactic systems encapsulated within the dendritic polymer. When used in combination with 2-PAM and atropine, the dendritic encapsuled OPAA provided a 25 ×LD50 protection against DFP intoxication, while the similarly constructed OPH complex showed a more dramatic protection (780 ×LD50) against paraoxon intoxication in Balb/c mice. The studies demonstrate a synergistic enhancement of the antagonist, since the antidotal protection of 2-PAM+atropine against DFP and paraoxon is approximately 8 and 60 ×LD50, respectively.

Original languageEnglish
Pages (from-to)85-92
Number of pages8
JournalNanotoxicology
Volume1
Issue number2
DOIs
Publication statusPublished - Jun 1 2007

    Fingerprint

Keywords

  • Dendritic polymers
  • Nanocapsules
  • Organophosphorus Acid Anhydrolase (OPAA)
  • Organophosphorus Hydrolase (OPH)
  • Organophosphorus antagonism

ASJC Scopus subject areas

  • Biomedical Engineering
  • Toxicology

Cite this

Petrikovics, I., Wales, M. E., Jaszberenyi, J. C., Budai, M., Baskin, S. I., Szilasi, M., Logue, B. A., Chapela, P., & Wild, J. R. (2007). Enzyme-based intravascular defense against organophosphorus neurotoxins: Synergism of dendritic-enzyme complexes with 2-PAM and atropine. Nanotoxicology, 1(2), 85-92. https://doi.org/10.1080/17435390500128271