Department of Mechanical Engineering, University of Alberta, Edmonton, AB, Canada.
Advanced Drug Delivery Group, Faculty of Pharmacy, University of Sydney, Sydney, Australia.
Pharm Res. 2017 Oct;34(10):2084-2096. doi: 10.1007/s11095-017-2213-4. Epub 2017 Jun 23.
To compare titer reduction and delivery rate of active anti-tuberculosis bacteriophage (phage) D29 with three inhalation devices.
Phage D29 lysate was amplified to a titer of 11.8 ± 0.3 log(pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalation devices: 1) vibrating mesh nebulizer; 2) jet nebulizer; 3) soft mist inhaler. Full-plate plaque assays, performed in triplicate at multiple dilution levels with the surrogate host Mycobacterium smegmatis, were used to quantify phage titer.
Respective titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 ± 0.1, 3.7 ± 0.1, and 0.6 ± 0.3 log(pfu/mL). Active phage delivery rate was significantly greater (p < 0.01) for the vibrating mesh nebulizer (3.3x10 ± 0.8x10 pfu/min) than for the jet nebulizer (5.4x10 ± 1.3x10 pfu/min). The soft mist inhaler delivered 4.6x10 ± 2.0x10 pfu per 11.6 ± 1.6 μL ex-actuator dose.
Delivering active phage requires a prudent choice of inhalation device. The jet nebulizer was not a good choice for aerosolizing phage D29 under the tested conditions, due to substantial titer reduction likely occurring during droplet production. The vibrating mesh nebulizer is recommended for animal inhalation studies requiring large amounts of D29 aerosol, whereas the soft mist inhaler may be useful for self-administration of D29 aerosol.
比较活性抗结核噬菌体（噬菌体）D29 在三种吸入装置中的滴度降低和输送率。
噬菌体 D29 裂解物扩增至 11.8 ± 0.3 log(pfu/mL)，并用等渗盐水稀释 1:100。过滤器捕获从三种类型的吸入装置中雾化的生理盐水 D29 制剂：1）振动网雾化器；2）射流雾化器；3）软雾吸入器。使用替代宿主耻垢分枝杆菌进行三次稀释水平的全板菌斑测定，以定量噬菌体滴度。
振动网雾化器、射流雾化器和软雾吸入器的相应滴度降低分别为 0.4 ± 0.1、3.7 ± 0.1 和 0.6 ± 0.3 log(pfu/mL)。活性噬菌体输送率显著更高（p < 0.01），振动网雾化器为 3.3x10 ± 0.8x10 pfu/min，而射流雾化器为 5.4x10 ± 1.3x10 pfu/min。软雾吸入器每 11.6 ± 1.6 μL 执行器剂量输送 4.6x10 ± 2.0x10 pfu。
输送活性噬菌体需要谨慎选择吸入装置。在测试条件下，射流雾化器不是雾化噬菌体 D29 的好选择，因为在液滴生成过程中可能会发生大量滴度降低。振动网雾化器推荐用于需要大量 D29 气溶胶的动物吸入研究，而软雾吸入器可能适用于 D29 气溶胶的自我给药。
