Nanoaerosols from Wick Electrospray for Improved Drug Delivery to Infants

描述（由申请人提供）：预计向接受机械通气的新生儿和婴儿输送雾化药物可提供许多益处，包括增加气道内作用部位的药物浓度、提高药物疗效和减少副作用。目前，针对各种医学状况递送给婴儿的气雾剂疗法的临床结果通常是令人失望的或不确定的。目前用于新生儿和婴儿机械通气的气雾剂生成技术已被证明可向肺部输送约1%或更少的初始剂量。据信，由于低递送效率和高剂量可变性，递送给婴儿的雾化药物通常无效。本研究的目的是开发一种新的基于吸液芯的电喷雾系统（WES），用于在有创机械通气期间将带静电的亚微米和纳米尺度气溶胶高效递送到新生儿和婴儿的呼吸道。与先前的用于气溶胶递送的装置相比， WES系统旨在产生亚微米（< 1000 nm）和纳米（< 100 nm）尺寸范围的气溶胶。气雾剂液滴的小尺寸将显著减少输送管线中的沉积，并允许大部分剂量进入气道。一旦进入肺内，电喷雾液滴的固有电荷以及纳米气溶胶的布朗运动将促进增强的沉积并确保几乎完全的肺滞留。与传统的电喷雾相比，WES装置用多孔聚合物芯取代了注射泵和毛细管，这降低了装置成本和复杂性。此外，典型的电喷雾装置的电晕针被移除，这消除了臭氧的形成。为了开发这种用于呼吸药物递送的新型装置，提出了以下具体目标。具体目标1：开发基于聚合物的吸液芯电喷雾（WES）系统，用于产生和输送带电的亚微米和纳米药用气雾剂。具体目标二：优化WES系统的性能，提高气雾剂输出速率，最大限度地减少设备和输送管路内的沉积。具体目标3：使用体外实验和CFD模拟评估WES气溶胶在婴儿呼吸道中的传输和沉积。所提出的装置将首次提供亚微米液滴源，具有最小的装置和输送管线沉积（< 20-30%）和气雾剂的完全肺保留，这代表与当前装置相比1至2个数量级的改进。其中改善对肺的递送效率、降低剂量变异性和在婴儿的整个气道内的沉积是至关重要的潜在应用包括使用雾化表面活性剂、抗生素、前列腺素类和利尿剂。

DESCRIPTION (provided by applicant): The delivery of aerosolized medications to neonates and infants on mechanical ventilation is expected to provide a number of benefits including increased drug concentrations at the site of action within the airways, improved drug efficacy, and reduced side effects. Presently, clinical outcomes of aerosol therapy delivered to infants for a variety of medical conditions are often disappointing or inconclusive. Current aerosol generation techniques for use with neonates and infants on mechanical ventilation have been shown to deliver approximately 1% or less of the initial dose to the lungs. It is believed that aerosolized medicines delivered to infants are often ineffective because of low delivery efficiencies and high dose variability. The objective of this study is to develop a new wick-based electrospray system (WES) for highly efficient delivery of electrostatically charged submicrometer and nanometer scale aerosols to the respiratory airways of neonates and infants during invasive mechanical ventilation. In contrast with previous devices for aerosol delivery, the WES system is intended to generate aerosols in the submicrometer (< 1000 nm) and nanometer (< 100 nm) size regimes. The small size of the aerosol droplets will dramatically reduce deposition in the delivery lines and allow a large fraction of the dose to enter the airways. Once inside the lungs, the inherent charge of the electrospray droplets as well as Brownian motion of the nanometer aerosol will foster enhanced deposition and ensure almost complete lung retention. Compared with conventional electrospray, the WES device replaces the syringe pump and capillary with a porous polymer wick, which reduces device cost and complexity. Furthermore, the corona needle of typical electrospray devices is removed, which eliminates the formation of ozone. In order to develop this novel device for respiratory drug delivery, the following specific aims are proposed. Specific Aim 1: Develop a polymer-based wick electrospray (WES) system for generating and delivering charged submicrometer and nanometer pharmaceutical aerosols. Specific Aim 2: Optimize the performance of the WES system in terms of increasing the aerosol output rate and minimizing deposition within the device and delivery lines. Specific Aim 3: Evaluate the transport and deposition of WES aerosols in the respiratory airways of infants using in vitro experiments and CFD simulations. The proposed device will provide, for the first time, a source of submicrometer droplets with minimal device and delivery line deposition (< 20-30%) and full lung retention of the aerosol, which represents a 1 to 2 order of magnitude improvement compared with current devices. Potential applications where improved delivery efficiency to the lungs, reduced dose variability, and deposition within the entire airways of infants are of critical importance include the use of aerosolized surfactants, antibiotics, prostanoids, and diuretics.