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提供雾化药物预计将提供许多好处，包括增加呼吸道内作用部位的药物浓度，改善药物疗效，减少副作用。目前，在各种医疗条件下为婴儿提供雾化疗法的临床结果往往令人失望或不确定。目前用于新生儿和婴儿机械通风的气雾剂生成技术已被证明可将大约1%或更少的初始剂量输送到肺部。人们认为，向婴儿提供雾化药物往往是无效的，因为给药效率低，剂量变异性大。本研究的目的是开发一种新型的基于灯芯的电喷雾系统(WES)，用于在有创机械通气过程中将带电的亚微米和纳米级气雾剂高效地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(&lt；1000 nm)和纳米(&lt；100 nm)尺寸的气溶胶。气雾滴的小尺寸将极大地减少输送管道中的沉积，并允许很大一部分剂量进入呼吸道。一旦进入肺部，电喷雾液滴的固有电荷以及纳米气雾剂的布朗运动将促进沉积，并确保几乎完全的肺滞留。与传统的电喷雾装置相比，WES装置用多孔聚合物芯取代了注射泵和毛细管，降低了装置成本和复杂性。此外，移除了典型电喷设备的电晕针，从而消除了臭氧的形成。为了开发这种新型的呼吸道给药装置，提出了以下具体目标。具体目标1：开发一种基于聚合物的芯电喷雾(WES)系统，用于产生和输送带电的亚微米和纳米药物气雾剂。具体目标2：优化WES系统的性能，以增加气雾剂输出率并最大限度地减少设备和输送管道内的沉积。具体目标3：利用体外实验和CFD模拟评估WES气溶胶在婴儿呼吸道中的传输和沉积。该装置将首次以最小的装置和传送线沉积(&lt；20%-30%)提供亚微米级的液滴来源，以及气雾剂在肺中的完全滞留，这与目前的装置相比有1到2个数量级的改进。潜在的应用包括使用雾化表面活性物质、抗生素、前列腺素类药物和利尿剂，提高对肺部的输送效率、降低剂量变异性和婴儿整个呼吸道内的沉积至关重要。 公共卫生相关性：目前用于通过机械通气向婴儿输送雾化药物的设备在连接管中损失了大量给药剂量，因此只有大约1%的药物到达患者的肺部。在这项研究中，聚合物芯和电喷雾相结合来生产纳米级气雾剂，与传统系统相比，这种气雾剂将肺部的输送效率提高了10到100倍。预计提高交付效率和减少变异性 剂量将使目前的许多吸入性药物更有效，并可能允许婴儿使用吸入性抗生素和表面活性物质。