Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK.
Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK.
Int J Pharm. 2024 Dec 5;666:124772. doi: 10.1016/j.ijpharm.2024.124772. Epub 2024 Sep 27.
Nebulized lung surfactant therapy has been a neonatology long-pursued goal. Nevertheless, many clinical trials have yet to show a clear clinical efficacy of nebulized surfactant, which, in part, is due to the technical challenges of delivering aerosols to the lungs of preterm neonates. The study aimed to test microbubbles for improving lung deposition in preterm neonates. An in vitro testing method was developed to replicate the clinical environment; it used a 3D-printed preterm neonate model, connected to a high-flow nasal cannula (HFNC) and a vibrating mesh nebulizer. The flow rate of the HFNC mirrored that used in the clinics (i.e., 4, 6, and 8 L/min). Followingly, the lung penetrations of aerosols with and without microbubbles were compared. The aerodynamic diameter of aerosols with microbubbles (MMAD=1.75 μm) was lower than that of the counterpart (MMAD=2.25 μm). Microbubble-laden aerosols had a significantly higher number of microbubbles that were below 1.0 μm. Microbubble-laden aerosols had dramatically higher lung penetration in the preterm model; lung penetration efficiencies were 30.0, 25.5, and 17.5 % at 4, 6, and 8 L/min, respectively, whereas the lung penetration efficiency for conventionally nebulized aerosols was below 1.25 % in the three flow rates.
雾化肺表面活性剂治疗一直是新生儿学长期追求的目标。然而，许多临床试验尚未显示出雾化表面活性剂的明确临床疗效，部分原因是向早产儿肺部输送气雾剂存在技术挑战。本研究旨在测试微泡以改善早产儿的肺部沉积。开发了一种体外测试方法来复制临床环境；它使用了一个 3D 打印的早产儿模型，连接到高流量鼻导管 (HFNC) 和振动网式雾化器。HFNC 的流速与临床使用的流速（即 4、6 和 8 L/min）相匹配。随后，比较了有和没有微泡的气雾剂的肺部渗透情况。有微泡的气雾剂的空气动力学直径（MMAD=1.75μm）低于对照气雾剂（MMAD=2.25μm）。载入微泡的气雾剂中，直径小于 1.0μm 的微泡数量明显更多。载入微泡的气雾剂在早产儿模型中的肺部穿透率显著更高；在 4、6 和 8 L/min 时，肺穿透效率分别为 30.0%、25.5%和 17.5%，而传统雾化气雾剂在三种流速下的肺穿透效率均低于 1.25%。
