Lipsome-formulated enzymes for organophosphate scavenging: butyrylcholinesterase and Demeton-S.
Butyrylcholinesterase-encapsulating bioadhesive liposomes are investigated as prophylactic scavengers of organophosphates for local administration to skin, eyes, airways, and lungs-gates through which organophosphates penetrate living systems. The systems were optimized with respect to: encapsulation efficiency; type of bioadhesive ligand bound to liposomes (collagen or hyaluronan); ligand density at the liposomal surface; retention of encapsulated-enzyme activity; protection of encapsulated enzyme from proteolysis; and scavenging the model organophosphate Demeton-S (DS). Monolayers of PC-12 cells were selected for feasibility testing based on: high affinity binding of the bioadhesive liposomes-DeltaG0 release upon binding ranged from -9 to -12 kcal/mol ligand; ability to mimic an organophosphate attack upon intact cells and measuring its impact on intracellular acetylcholinesterase. Under attack, unprotected cells lost 80-90% of intracellular enzyme activity. The loss was reduced to 20-30% for protected cells (pre-treated with the formulations), at the expense of liposomal Butyrylcholinesterase. These results support our prophylactic approach.
Fischer
Sharon
S
Department of Biochemistry, Tel Aviv University, Tel Aviv 69978, Israel.
Arad
Aya
A
Margalit
Rimona
R
D000269:Adhesives; D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D002091:Butyrylcholinesterase / Q000008:administration & dosage* / Q000378:metabolism; D002619:Chemical Warfare Agents / Q000633:toxicity; D003094:Collagen; D004337:Drug Carriers; D006820:Hyaluronic Acid; D008081:Liposomes; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D010755:Organophosphates / Q000037:antagonists & inhibitors / Q000633:toxicity; D063086:Organothiophosphates / Q000037:antagonists & inhibitors* / Q000633:toxicity; D016716:PC12 Cells; D051381:Rats
D000269:Adhesives; D002619:Chemical Warfare Agents; D004337:Drug Carriers; D008081:Liposomes; D009498:Neurotoxins; D010755:Organophosphates; D063086:Organothiophosphates; D006820:Hyaluronic Acid; D003094:Collagen; D002091:Butyrylcholinesterase; C030064:demeton-S-methyl