Lipsome-formulated enzymes for organophosphate scavenging: Butyrylcholinesterase and Demeton-S

Sharon Fischer, Aya Arad, Rimona Margalit

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)108-115
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume434
Issue number1 SPEC. ISS.
DOIs
StatePublished - 1 Feb 2005

Keywords

  • Acetylcholinesterase
  • Bioadhesive liposomes
  • Butyrylcholinesterase
  • Demeton-S
  • Organophosphates
  • Prophylaxis

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