title: Creation of a protective pulmonary bioshield against inhaled organophosphates using an aerosolized bioscavenger.
abstract: In addition to the global use of organophosphate (OP) pesticides for agriculture, OP nerve agents and pesticides have been employed on battlefields and by terrorists (e.g., a recent sarin attack in Syria). These occurrences highlight the need for an effective countermeasure against OP exposure. Human butyrylcholinesterase (HuBChE) is a leading candidate, but injection of the high doses required for protection present pharmacokinetic challenges. An aerosolized recombinant form (aer-rHuBChE) that can neutralize inhaled OPs at the portal of entry has been assessed for its efficacy in protecting macaques against respiratory toxicity following inhalation exposure to the pesticide paraoxon (aer-Px). While protection in macaques has been demonstrated using the MicroSprayer® delivery device, administration to humans will likely employ a vibrating mesh nebulizer (VMN). Compared to the 50-70% lung deposition achieved in adult humans with a VMN, deposition in macaques is <5%, an initial major obstacle to demonstrating protection. Such problems have been partly overcome by using a more efficient modified VMN and proportionally higher doses, which together generate an effective rHuBChE pulmonary bioshield and protect against high levels of inhaled Px.
authors.affiliation: PlantVax Inc, Rockville, Maryland.
authors.forename: Yvonne J
authors.initials: YJ
authors.lastname: Rosenberg
authors.affiliation: Department of Respiratory Care, Georgia State, University, Atlanta, Georgia.
authors.forename: James B
authors.initials: JB
authors.lastname: Fink
mesh_terms: D000336:Aerosols / Q000494:pharmacology*; D000818:Animals; D016503:Drug Delivery Systems; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D009943:Organophosphorus Compounds / Q000633:toxicity*; D020011:Protective Agents / Q000494:pharmacology*
chemical_list: D000336:Aerosols; D009943:Organophosphorus Compounds; D020011:Protective Agents
keywords: butyrylcholinesterase; inhaled neurotoxins; macaques; protection; pulmonary