TY - JOUR
T1 - Lipsome-formulated enzymes for organophosphate scavenging
T2 - Butyrylcholinesterase and Demeton-S
AU - Fischer, Sharon
AU - Arad, Aya
AU - Margalit, Rimona
PY - 2005/2/1
Y1 - 2005/2/1
N2 - 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-ΔG0 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.
AB - 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-ΔG0 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.
KW - Acetylcholinesterase
KW - Bioadhesive liposomes
KW - Butyrylcholinesterase
KW - Demeton-S
KW - Organophosphates
KW - Prophylaxis
UR - http://www.scopus.com/inward/record.url?scp=11144270154&partnerID=8YFLogxK
U2 - 10.1016/j.abb.2004.10.029
DO - 10.1016/j.abb.2004.10.029
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AN - SCOPUS:11144270154
SN - 0003-9861
VL - 434
SP - 108
EP - 115
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 1 SPEC. ISS.
ER -