TY - JOUR PY - 2016// TI - Creation of a protective pulmonary bioshield against inhaled organophosphates using an aerosolized bioscavenger JO - Annals of the New York Academy of Sciences A1 - Rosenberg, Yvonne J. A1 - Fink, James B. SP - 151 EP - 158 VL - 1374 IS - 1 N2 - 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.

© 2016 New York Academy of Sciences.

Language: en

LA - en SN - 0077-8923 UR - http://dx.doi.org/10.1111/nyas.13106 ID - ref1 ER -