The delivery of pharmaceutical aerosols to infants receiving mechanical ventilation is extremely challenging due to small diameter flow passages, low tidal volumes, and frequent exhalation of the aerosol. The use of small charged particles is proposed as a novel method to prevent deposition in ventilator components and foster deposition in the lower infant airways. The objective of this study was to compare the performance of multiple new devices for generating small charged particles that are expected to maximize respiratory drug delivery in ventilated infants. Criteria used to select a leading device included production of a charged aerosol with a mass median aerodynamic diameter (MMAD) ≤ approximately 1.8 μm; low device depositional loss of the aerosol (<20%); particle charge in the range of the Rayleigh limit/100; and high drug output with low performance variability. Proposed new devices were a wick electrospray (WES) system with accelerated cross-flow air; a condensational vapor (CV) system with a charged solution and strong field gradient; and a low flow - induction charger (LF-IC) designed to operate with a modified commercial mesh nebulizer. Based on infant ventilation conditions, flow rates through the devices were in a range of 2-5 L/min and the devices were assessed in terms of depositional drug loss and emitted drug mass; droplet size distribution (DSD) using a Mini-MOUDI; and DSD and net charge with a modified ELPI. Considering the WES, primary limitations were (i) low and variable aerosol production rates and (ii) high device depositional losses. The CV device produced a high quality aerosol with a MMAD of 0.14 μm and a drug delivery rate of 25 μg/min. However, the device was excluded because it failed to produce a charged aerosol. In contrast, the LF-IC produced a 1.6 μm aerosol with high net charge, low device depositional loss (<15% based on recovery), and low variability. In the ELPI size fraction bin nearest the MMAD, the LF-IC produced >100 elementary charges per particle, which was an order of magnitude increase compared to the case of zero charging voltage. In conclusion, the LF-IC was selected as a leading system that is expected to improve aerosol delivery efficiency in ventilated infants through the use of small charged particles.

中文翻译：

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产生带电药物气雾剂，旨在改善通气婴儿的靶向药物输送


由于气流通道直径小、潮气量低以及气雾剂频繁呼出，向接受机械通气的婴儿输送药物气雾剂极具挑战性。提出使用小带电粒子作为一种新方法来防止呼吸机部件中的沉积并促进婴儿下呼吸道中的沉积。本研究的目的是比较多种产生小带电粒子的新设备的性能，这些设备有望最大限度地提高通气婴儿的呼吸药物输送。用于选择领先设备的标准包括产生质量中值空气动力学直径 (MMAD) ≤ 约 1.8 μm 的带电气雾剂；气溶胶的设备沉积损失低（<20 id=19>每个颗粒 100 个基本电荷，与零充电电压的情况相比，增加了一个数量级。总之，LF-IC 被选为领先系统，预计通过使用小带电粒子来提高通气婴儿的气雾输送效率。