In vitro evaluation of the potential use of snake-derived peptides in the treatment of respiratory infections using inhalation therapy: A proof of concept study
In vitro evaluation of the potential use of snake-derived peptides in the treatment of respiratory infections using inhalation therapy: A proof of concept study
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DOI：
10.1016/j.ejps.2023.106398
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发表时间：
2023-02-08
影响因子：
4.6
通讯作者：
Taggart，Clifford C.
中科院分区：
文献类型：
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作者：
Creane，Shannice;Joyce，Mary;Taggart，Clifford C.
使用雾化器的吸入疗法是用于药物递送的有吸引力的非侵入性途径，特别是用于用抗炎和抗微生物化合物治疗肺部感染。本研究评估了三种蛇源性肽（称为Sn 1b，SnE 1和SnE 1-F）的适用性，我们最近已经证明这些肽具有有效的抗炎和抑菌活性，用于使用振动网孔雾化器（VMN）进行雾化。在进行空气动力学粒度分布之前，在模拟成人自主呼吸和机械通气患者模型中评估雾化对肽浓度、稳定性和功能的影响。当雾化时，所有三种肽表现出与其非雾化对应物相似的功能，并且发现在模拟机械通气期间是可吸入的。基于使用下一代撞击器（NGI）对雾化肽的液滴分布的评估，证明如果在体内施用，则每种肽将可能被递送至下气道。这些数据表明，使用VMN的雾化是靶向微生物呼吸道感染，甚至可能是全身感染的抗微生物/抗炎肽递送的可行手段。
Inhalation therapy using nebulisers is an attractive non-invasive route for drug delivery, particularly for the treatment of lung infections with anti-inflammatory and anti-microbial compounds. This study evaluated the suitability of three snake-derived peptides (termed Sn1b, SnE1 and SnE1-F), which we have recently shown have potent anti-inflammatory and bacteriostatic activities, for nebulisation using a vibrating mesh nebuliser (VMN). The effect of nebulisation on peptide concentration, stability and function were assessed, prior to progression to aerodynamic particle size distribution, andin vitrodrug delivery in simulated adult spontaneous breathing and mechanical ventilated patient models. When nebulised, all three peptides exhibited similar functions to their non-nebulised counterparts and were found to be respirable during simulated mechanical ventilation. Based on the assessment of the droplet distributions of nebulised peptides using a Next Generation Impactor (NGI) demonstrated that if administeredin vivoeach peptide would likely be delivered to the lower airways. These data suggest that nebulisation using a VMN is a viable means of anti-microbial / anti-inflammatory peptide delivery targeting microbial respiratory infections, and possibly even systemic infections.