Creation of a protective pulmonary bioshield against inhaled organophosphates using an aerosolized bioscavenger.
Creation of a protective pulmonary bioshield against inhaled organophosphates using an aerosolized bioscavenger.
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DOI：
10.1111/nyas.13106
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发表时间：
2016-06
影响因子：
5.2
通讯作者：
Fink JB
中科院分区：
文献类型：
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作者：
Rosenberg YJ;Fink JB
除了在全球范围内使用有机磷（OP）农药用于农业之外，OP神经毒剂和农药也被用于战场和恐怖分子（例如，叙利亚最近发生的沙林毒气袭击事件）。这些事件强调了对OP暴露采取有效对策的必要性。人丁酰胆碱酯酶（HuBChE）是一种主要的候选药物，但注射保护所需的高剂量存在药代动力学挑战。从（aer-rHuBChE），可以中和吸入的OP在其入口处的雾化重组已被评估其有效性，以保护猕猴对呼吸道毒性后，吸入暴露于农药对氧磷（aer-Px）。虽然已经证明使用微喷雾器递送装置在猕猴中具有保护作用，但向人类施用可能会使用振动网孔雾化器（VMN）。与在具有VMN的成年人中实现的50-70%肺沉积相比，猕猴中的沉积<5%，这是证明保护的最初主要障碍。通过使用更有效的改良VMN和成比例的更高剂量，这些问题已部分克服，它们一起产生有效的rHuBChE肺生物屏障并防止高水平的吸入Px。
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., the 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 from (aer-rHuBChE) that can neutralize inhaled OPs at their portal of entry has been assessed for its efficacy to protect macaques against respiratory toxicity following inhalation exposure to the pesticide paraoxon (aer-Px). While protection in macaques has been demonstrated using a 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.