Add time:09/24/2019 Source:sciencedirect.com
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.
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