Journal Article

Long Circulating Liposomes Encapsulating Organophosphorus Acid Anhydrolase in Diisopropylfluorophosphate Antagonism

I. Petrikovics, T.-C. Cheng, D. Papahadjopoulos, K. Hong, R. Yin, J. J. DeFrank, J. Jaing, Z. H. Song, W. D. McGuinn, D. Sylvester, L. Pei, J. Madec, C. Tamulinas, J. C. Jaszberenyi, T. Barcza and J. L. Way

in Toxicological Sciences

Volume 57, issue 1, pages 16-21
Published in print September 2000 | ISSN: 1096-6080
Published online September 2000 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/57.1.16
Long Circulating Liposomes Encapsulating Organophosphorus Acid Anhydrolase in Diisopropylfluorophosphate Antagonism

More Like This

Show all results sharing these subjects:

  • Medical Toxicology
  • Toxicology (Non-medical)

GO

Show Summary Details

Preview

These studies are focused on antagonizing organophosphorous (OP) intoxications by a new conceptual approach using recombinant enzymes encapsulated within sterically stabilized liposomes to enhance diisopropylfluorophosphate (DFP) degradation. The OP hydrolyzing enzyme, organophosphorous acid anhydrolase (OPAA), encapsulated within the liposomes, was employed either alone or in combination with pralidoxime (2-PAM) and/or atropine. The recombinant OPAA enzyme, from the Alteromonas strain JD6, has high substrate specificity toward a wide range of OP compounds, e.g., DFP, soman, and sarin. The rate of DFP hydrolysis by liposomes containing OPAA (SL)* was measured by determining the changes in fluoride-ion concentration using a fluoride ion-selective electrode. This enzyme carrier system serves as a biodegradable protective environment for the OP-metabolizing enzyme (OPAA), resulting in an enhanced antidotal protection against the lethal effects of DFP. Free OPAA alone showed some antidotal protection; however, the protection with 2-PAM and/or atropine was greatly enhanced when combined with (SL)*.

Keywords: phosphotriesterase; OPA anhydrase; OPAA; DFP antagonism; sterically stabilized liposomes; OP hydrolase (OPH); organophosphorus antagonism; stealth liposomes; long circulating liposomes

Journal Article.  4177 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.