Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
J Aerosol Med Pulm Drug Deliv. 2012 Oct;25(5):290-6. doi: 10.1089/jamp.2011.0920. Epub 2012 Mar 6.
Aerodynamic forces provide the primary means of distributing aerosol medications within the lungs. Partial airway obstructions can limit both air flow and aerosol penetration into diseased zones. We hypothesize that low surface tension additives may help to disperse aerosol medications after deposition in the airways, improving dose uniformity and drug delivery to underventilated regions. To test this, we performed a pilot scintigraphy study of surfactant and saline deposition and postdeposition dispersion.
Because inhaled antibiotics for cystic fibrosis provide an example of where self-dispersing medications may be useful, we administered calfactant and saline aerosols with added Technetium 99m sulfur colloid (Tc-SC; 100 nm filtered) on different days in randomized order to eight cystic fibrosis (CF) subjects (average FEV(1)%, p=85 ± 12%). Nebulized delivery was matched (similar aerosol sizes and volume delivery rates, fixed breathing patterns). Tc-SC distribution in the lungs was imaged continuously for 30 min after delivery.
Both aerosols were well tolerated. Aerosol distribution was mostly peripheral (58/42%) and initially similar for saline and surfactant. Changes in whole lung counts after 30 min were also similar. Peripheral lung activity decreased more rapidly on average with calfactant though the difference versus saline was not statistically significant. Central to peripheral count ratio decreased with saline and increased with calfactant and c/p changes approached significance (-0.05 ± 0.16 vs. 0.10 ± 0.10; p=0.07 Wilcoxon).
Our results lack statistical significance, but suggest that inhaled calfactant increased peripheral clearance, due to either surfactant-based dispersion or mucociliary effects. Further studies are needed to define the potential for low surface tension carriers to improve drug delivery.
空气动力学力是将气雾剂药物分布在肺部的主要手段。部分气道阻塞会限制气流和气雾剂渗透到患病区域。我们假设低表面张力添加剂可以帮助在气道沉积后分散气雾剂药物,从而提高剂量均匀性和向通气不足区域输送药物的效果。为了验证这一点,我们进行了一项表面活性剂和盐水沉积及沉积后分散的试点闪烁扫描研究。
由于吸入性抗生素治疗囊性纤维化提供了一个自分散药物可能有用的例子,我们在不同的日子里以随机顺序向八位囊性纤维化(CF)患者(平均 FEV1%,p=85±12%)施用卡泊芬净和添加锝 99m 硫胶体(Tc-SC;100nm 过滤)的盐水气雾剂。雾化输送匹配(气溶胶大小和体积输送率相似,固定呼吸模式)。在输送后连续 30 分钟对肺部 Tc-SC 分布进行连续成像。
两种气雾剂均耐受良好。气雾剂分布主要在周边(58/42%),盐水和表面活性剂初始分布相似。30 分钟后全肺计数的变化也相似。尽管卡泊芬净与盐水相比差异无统计学意义,但卡泊芬净的外周肺活性平均下降更快。中央到外周计数比随着盐水下降而增加,随着卡泊芬净增加而增加,c/p 变化接近显著(-0.05±0.16 与 0.10±0.10;p=0.07 Wilcoxon)。
我们的结果缺乏统计学意义,但表明吸入性卡泊芬净增加了外周清除率,这归因于基于表面活性剂的分散或黏液纤毛作用。需要进一步研究来确定低表面张力载体改善药物输送的潜力。