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

• 批准号: 8358410
• 负责人: P. Worth Longest
• 金额: $ 16.98万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-05 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358410
• 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

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. PUBLIC HEALTH RELEVANCE: Current devices for delivering aerosolized medicines to infants on mechanical ventilation lose a large amount of the administered dose in the connective tubing, such that only approximately 1% of the drug reaches the patient's lungs. In this study, polymer wicks and electrospray are combined to produce nanometer-scale aerosols that increase delivery efficiency to the lungs by a factor ranging between 10 and 100 compared with conventional systems. It is expected that improving delivery efficiency and reducing variability in dose will make many current inhaled medications more effective and may allow for the use of inhaled antibiotics and surfactants in infants.

描述（由申请人提供）：通过机械通气向新生儿和婴儿输送雾化药物预计会带来许多好处，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，针对各种疾病的婴儿进行气雾疗法的临床结果常常令人失望或不确定。目前用于新生儿和婴儿机械通气的气雾生成技术已被证明可以向肺部输送约 1% 或更少的初始剂量。据信，由于递送效率低和剂量变异性大，递送给婴儿的雾化药物常常无效。本研究的目的是开发一种新型基于灯芯的电喷雾系统（WES），用于在有创机械通气期间高效地将带静电的亚微米和纳米级气溶胶输送到新生儿和婴儿的呼吸道。与以前的气雾剂输送装置相比， WES 系统旨在产生亚微米（< 1000 nm）和纳米（< 100 nm）尺寸的气溶胶。气溶胶液滴的小尺寸将大大减少输送管线中的沉积，并允许大部分剂量进入气道。一旦进入肺部，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部保留。与传统电喷雾相比，WES装置用多孔聚合物吸芯取代了注射泵和毛细管，降低了装置成本和复杂性。此外，典型电喷雾装置的电晕针被移除，从而消除了臭氧的形成。为了开发这种新型呼吸药物输送装置，提出了以下具体目标。具体目标 1：开发基于聚合物的灯芯电喷雾 (WES) 系统，用于生成和输送带电的亚微米和纳米药物气溶胶。具体目标 2：在提高气溶胶输出率并最大限度地减少设备和输送管线内的沉积方面优化 WES 系统的性能。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输送和沉积。所提出的装置将首次提供亚微米液滴源，具有最少的装置和输送管线沉积（< 20-30%）和气溶胶的完全肺保留，这与传统的装置相比提高了 1 到 2 个数量级。当前设备。提高肺部输送效率、减少剂量变异性和婴儿整个气道内的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。 公共健康相关性：目前用于通过机械通气向婴儿输送雾化药物的装置会在连接管道中损失大量给药剂量，因此只有大约 1% 的药物到达患者的肺部。在这项研究中，聚合物吸芯和电喷雾相结合产生纳米级气雾剂，与传统系统相比，可将肺部输送效率提高 10 至 100 倍。预计将提高交付效率并减少可变性 剂量将使许多目前的吸入药物更有效，并可能允许在婴儿中使用吸入抗生素和表面活性剂。