In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism.
This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.
Petrikovics
I
I
Department of Medical Pharmacology and Toxicology, Texas A&M University, College of Medicine, College Station 77843-1114, USA.
McGuinn
W D
WD
Sylvester
D
D
Yuzapavik
P
P
Jiang
J
J
Way
J L
JL
Papahadjopoulos
D
D
Hong
K
K
Yin
R
R
Cheng
T C
TC
DeFrank
J J
JJ
D000818:Animals; D000931:Antidotes / Q000008:administration & dosage*; D043303:Aryldialkylphosphatase; D001285:Atropine / Q000494:pharmacology; D004950:Esterases / Q000008:administration & dosage*; D006868:Hydrolysis; D007531:Isoflurophate / Q000493:pharmacokinetics; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D062025:Organophosphate Poisoning; D011220:Pralidoxime Compounds / Q000494:pharmacology; D011994:Recombinant Proteins / Q000008:administration & dosage
D000931:Antidotes; D008081:Liposomes; D011220:Pralidoxime Compounds; D011994:Recombinant Proteins; D007531:Isoflurophate; D001285:Atropine; D004950:Esterases; D043303:Aryldialkylphosphatase; C028797:pralidoxime