Prevention of Organophosphorous Lethality with OPA Anhydrolase (OPAA-2) Containing Stealth Liposomes
Abstract
This research is focused on the use of various liposome-like drug carrier systems containing recombinant organophosphorus (OP) hydrolyzing enzymes (OPH = Organophosphorus Acid Hydrolase; OPAA = Organophosphorus Acid Anhydrolase) to prevent organophosphorus poisoning. The objective is to provide long term protection against OP intoxication by using OP-hydrolyzing enzymes with various liposome-based enzyme carrier Systems such as sterically stabilized liposomes (SL) and modified liposome-like carriers (NT). Present research is focused on: studying and optimizing of the in vitro efficacy of the OP-comlex-hydrolyzing enzymes; optimizing the carrier systems; studying the in vivo efficacy of the encapsulated enzymes; studying the blood cholinesterase level in the presence of OPs, 2-PAM, and the OP-hydrolyzing enzymes and to monitor and attempt to predict the OP toxicity and antagonism. OPH enzyme has, highly efficient substrate specificity to paraoxon but in general it is less efficient to diisopropylfluorophosphate (DFP), soman and satin. However, OPAA can hydrolyze DFP, soman and satin with a relatively high efficiency. DFP and paraoxon were used as model substrates to study the in vitro OP-hydrolyzing efficiency and the in vivo antidotal efficiency of the encapsulated OPAA and OPH. Hydrolysis of DFP was followed by measuring the amount of the fluoride ions formed by using a fluoride ion selective electrode, Hydrolysis of paraoxon was determined spectrophotometrically by measuring the p-nitrophenol formation. The paraoxon hydrolysis displayed saturation kinetics with increasing substrate concentration both with free OPH and encapsulated OPH. The kinetic parameters suggest that paraoxon can freely enter and exit the enzyme carrier systems. Preliminary toxicology studies indicate that the encapsulated OPH and OPAA, (NT-OPH and NT-OPAA), may strikingly enhance the antidotal effects of the clinically proven OP antidotes, 2-PAM and atropine.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2001
- Accession Number
- ADA398208
Entities
People
- James Leong-way
Organizations
- Texas A&M University