Generating Charged Pharmaceutical Aerosols Intended to Improve Targeted Drug Delivery in Ventilated Infants.
Generating Charged Pharmaceutical Aerosols Intended to Improve Targeted Drug Delivery in Ventilated Infants.
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DOI：
10.1016/j.jaerosci.2015.05.015
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发表时间：
2015-10-01
影响因子：
4.5
通讯作者：
Longest PW
中科院分区：
文献类型：
--
作者：
Holbrook L;Hindle M;Longest PW
向接受机械通气的婴儿递送药物气雾剂是极其具有挑战性的，这是由于小直径的流动通道、低潮气量和气雾剂的频繁呼出。提出使用小带电粒子作为防止呼吸机部件中沉积和促进下婴儿气道中沉积的新方法。本研究的目的是比较多种新器械产生小带电粒子的性能，这些小带电粒子有望最大限度地提高通气婴儿的呼吸药物输送。用于选择领先器械的标准包括：产生质量中值空气动力学直径（MMAD）≤约1.8 μm的带电气雾剂;气雾剂的器械沉积损失低（<20%）;颗粒电荷在瑞利极限/100范围内;以及药物输出高，性能变异性低。提出的新装置是具有加速横流空气的芯式电喷雾（WES）系统;具有带电溶液和强场梯度的冷凝蒸汽（CV）系统;以及设计成与经修改的商业网状雾化器一起操作的低流量感应充电器（LF-IC）。基于婴儿通气条件，通过装置的流速在2-5 L/min的范围内，并根据沉积药物损失和释放的药物质量、使用Mini-MOUDI的液滴尺寸分布（DSD）以及使用改良ELPI的DSD和净电荷对装置进行评估。考虑到WES，主要限制是（i）低且可变的气溶胶产生速率和（ii）高的装置沉积损失。CV装置产生了高质量的气雾剂，MMAD为0.14 μm，药物递送速率为25 μg/min。但是，该装置被排除在外，因为它无法产生带电气雾剂。相比之下，LF-IC产生的1.6 μm气溶胶具有高净电荷、低设备沉积损失（基于回收率<15%）和低可变性。在最接近MMAD的ELPI尺寸分数箱中，LF-IC产生>100个基本电荷/颗粒，这与零充电电压的情况相比增加了一个数量级。总之，LF-IC被选为领先的系统，有望通过使用小的带电粒子来提高通气婴儿的气雾剂输送效率。
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.