Nanoaerosols from Wick Electrospray for Improved Drug Delivery to Infants

来自灯芯电喷雾的纳米气溶胶可改善婴儿的药物输送

基本信息

批准号：
8520366
负责人：
P. Worth Longest
金额：
$ 20.62万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-05 至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8520366
关键词：
Adult Adverse effects Aerosol Drug Therapy Aerosols Alveolar Anti-Infective Agents Antibiotics Biological Availability Blood capillaries Breathing Caliber Charge Clinical Clinical Research Deposition Devices Diuretics Dose Drug Delivery Systems Electrostatics Ensure Exhalation Fostering Generations Glucocorticoids In Vitro Infant Liquid substance Lung Measurable Mechanical ventilation Medical Medicine Microprocessor Monobactams Motion Needles Neonatal Outcome Output Ozone Particle Size Patients Performance Pharmaceutical Preparations Pharmacologic Substance Polymers Power Sources Production Prostaglandins Pump Reporting Site Source Syringes System Techniques Time Tracheobronchial Tube aerosolized base capillary cost drug efficacy endotracheal improved nanometer nanoscale neonate novel particle research study respiratory simulation surfactant uptake

项目摘要

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.

描述（由申请人提供）：预计向新生儿和婴儿提供的雾化药物将提供许多好处，包括在气道内部的作用部位增加药物浓度，提高药物疗效和副作用降低。目前，为各种医疗疾病的婴儿提供的气溶胶疗法的临床结果通常令人失望或不确定。当前与新生儿一起使用的气溶胶生成技术已证明在机械通气中可将初始剂量的初始剂量的大约1％或以下提供给肺部。据认为，由于递送效率低和高剂量的可变性，送给婴儿的雾化药通常是无效的。这项研究的目的是开发一种新的基于WITW的电喷雾系统（WES），以高效地传递带电荷的亚微米和纳米尺度的气溶胶气溶胶向新生儿和婴儿的呼吸道通风期间，在侵入性机械通气过程中。与以前的气溶胶交付设备相反， WES系统旨在在亚微米（<1000 nm）和纳米表（<100 nm）尺寸状态下生成气溶胶。气溶胶液滴的小尺寸将大大减少递送线中的沉积，并让很大一部分剂量进入气道。一旦进入肺部，电喷雾液滴的固有电荷以及纳米气溶胶的布朗运动将增强沉积，并确保几乎完整的肺部保留。与传统的电喷雾相比，WES设备用多孔聚合物芯代替了注射器泵和毛细管，从而降低了设备的成本和复杂性。此外，除去了典型的电喷雾设备的电晕针，从而消除了臭氧的形成。为了开发这种新颖的呼吸道药物装置，提出了以下特定目的。特定目标1：开发基于聚合物的WITCE电喷雾（WES）系统，用于生成和传递带电的亚微米和纳米药物气溶胶。特定目标2：优化WES系统的性能，以增加气溶胶输出速率并最大程度地减少设备和输送线中的沉积。特定目的3：使用体外实验和CFD模拟评估婴儿气溶胶在婴儿呼吸道中的运输和沉积。所提出的设备将首次提供带有最小设备和输送线沉积（<20-30％）的亚微米液滴的来源，与电流设备相比，气溶胶的全肺保留为1到2个数量级。在整个婴儿气道中提高肺部递送效率，剂量变异性的降低以及沉积至关重要的潜在应用包括使用雾化表面活性剂，抗生素，前列腺素和利尿剂。