Long circulating liposomes encapsulating organophosphorus acid anhydrolase in diisopropylfluorophosphate antagonism.
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)*.
Petrikovics
I
I
Department of Medical Pharmacology and Toxicology, Texas A&M University, College of Medicine, College Station, Texas 77843-1114, USA.
Cheng
T C
TC
Papahadjopoulos
D
D
Hong
K
K
Yin
R
R
DeFrank
J J
JJ
Jaing
J
J
Song
Z H
ZH
McGuinn
W D
WD
Sylvester
D
D
Pei
L
L
Madec
J
J
Tamulinas
C
C
Jaszberenyi
J C
JC
Barcza
T
T
Way
J L
JL
D000818:Animals; D043303:Aryldialkylphosphatase; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004337:Drug Carriers; D004950:Esterases / Q000494:pharmacology*; D007531:Isoflurophate / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity*; D007928:Lethal Dose 50; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012524:Sarin / Q000378:metabolism; D012999:Soman / Q000378:metabolism; D013379:Substrate Specificity
D002800:Cholinesterase Inhibitors; D004337:Drug Carriers; D008081:Liposomes; D007531:Isoflurophate; D012999:Soman; D012524:Sarin; D004950:Esterases; D043303:Aryldialkylphosphatase