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:8358410
- 负责人:
- 金额:$ 16.98万
- 依托单位:
- 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 2014-07-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAdverse effectsAerosol Drug TherapyAerosolsAlveolarAnti-Infective AgentsAntibioticsBiological AvailabilityBlood capillariesBreathingCaliberChargeClinicalClinical ResearchDepositionDevicesDiureticsDoseDrug Delivery SystemsElectrostaticsEnsureExhalationFosteringGenerationsGlucocorticoidsIn VitroInfantLiquid substanceLungMeasurableMechanical ventilationMedicalMedicineMicroprocessorMonobactamsMotionNeedlesNeonatalOutcomeOutputOzoneParticle SizePatientsPerformancePharmaceutical PreparationsPharmacologic SubstancePolymersPower SourcesProductionProstaglandinsPumpReportingSiteSourceSyringesSystemTechniquesTimeTracheobronchialTubeaerosolizedbasecapillarycostdrug efficacyendotrachealimprovednanometernanoscaleneonatenovelparticleresearch studyrespiratorysimulationsurfactantuptake
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.
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):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。人们认为,由于输送效率低和剂量变异性大,向婴儿输送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。
公共卫生关系:目前用于向机械通气的婴儿递送雾化药物的装置在连接管中损失了大量的给药剂量,使得只有大约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,产生纳米级的气溶胶,与传统系统相比,将输送到肺部的效率提高了10到100倍。预计提高交付效率和减少
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。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
P. Worth Longest其他文献
P. Worth Longest的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('P. Worth Longest', 18)}}的其他基金
Preclinical development of a synthetic lung surfactant dry powder aerosol for hypoxemia or acute respiratory distress syndrome patients receiving different modes of ventilation support
用于接受不同通气支持模式的低氧血症或急性呼吸窘迫综合征患者的合成肺表面活性剂干粉气雾剂的临床前开发
- 批准号:
10658610 - 财政年份:2023
- 资助金额:
$ 16.98万 - 项目类别:
Preclinical development of a synthetic lung surfactant dry powder aerosol for acute respiratory distress syndrome patients receiving different modes of ventilation support
用于接受不同通气支持模式的急性呼吸窘迫综合征患者的合成肺表面活性剂干粉气雾剂的临床前开发
- 批准号:
10704308 - 财政年份:2022
- 资助金额:
$ 16.98万 - 项目类别:
Computational Fluid Dynamics (CFD) Models to Aid the Development of Generic Metered Dose Inhalers
计算流体动力学 (CFD) 模型有助于通用计量吸入器的开发
- 批准号:
10372282 - 财政年份:2021
- 资助金额:
$ 16.98万 - 项目类别:
Computational Fluid Dynamics (CFD) Models to Aid the Development of Generic Metered Dose Inhalers
计算流体动力学 (CFD) 模型有助于通用计量吸入器的开发
- 批准号:
10459405 - 财政年份:2021
- 资助金额:
$ 16.98万 - 项目类别:
Computational Fluid Dynamics (CFD) Models to Aid the Development of Generic Metered Dose Inhalers
计算流体动力学 (CFD) 模型有助于通用计量吸入器的开发
- 批准号:
10898102 - 财政年份:2021
- 资助金额:
$ 16.98万 - 项目类别:
Predictive Lung Deposition Models for Safety and Efficacy of Orally Inhaled Drug
口服吸入药物安全性和有效性的预测肺沉积模型
- 批准号:
8922803 - 财政年份:2012
- 资助金额:
$ 16.98万 - 项目类别:
Predictive Lung Deposition Models for Safety and Efficacy of Orally Inhaled Drug
口服吸入药物安全性和有效性的预测肺沉积模型
- 批准号:
8485977 - 财政年份:2012
- 资助金额:
$ 16.98万 - 项目类别:
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:
8520366 - 财政年份:2012
- 资助金额:
$ 16.98万 - 项目类别:
Improved Lung Delivery of Medical Aerosols through Enhanced Condensation Growth
通过增强冷凝增长改善医用气雾剂的肺部输送
- 批准号:
7573264 - 财政年份:2009
- 资助金额:
$ 16.98万 - 项目类别:
Improved Lung Delivery of Medical Aerosols through Enhanced Condensation Growth
通过增强冷凝增长改善医用气雾剂的肺部输送
- 批准号:
7760144 - 财政年份:2009
- 资助金额:
$ 16.98万 - 项目类别:
相似海外基金
Unraveling Adverse Effects of Checkpoint Inhibitors Using iPSC-derived Cardiac Organoids
使用 iPSC 衍生的心脏类器官揭示检查点抑制剂的副作用
- 批准号:
10591918 - 财政年份:2023
- 资助金额:
$ 16.98万 - 项目类别:
Optimization of mRNA-LNP vaccine for attenuating adverse effects and analysis of mechanism behind adverse effects
mRNA-LNP疫苗减轻不良反应的优化及不良反应机制分析
- 批准号:
23K15383 - 财政年份:2023
- 资助金额:
$ 16.98万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Elucidation of adverse effects of combined exposure to low-dose chemicals in the living environment on allergic diseases and attempts to reduce allergy
阐明生活环境中低剂量化学品联合暴露对过敏性疾病的不良影响并尝试减少过敏
- 批准号:
23H03556 - 财政年份:2023
- 资助金额:
$ 16.98万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Green tea-based nano-enhancer as an adjuvant for amplified efficacy and reduced adverse effects in anti-angiogenic drug treatments
基于绿茶的纳米增强剂作为抗血管生成药物治疗中增强疗效并减少不良反应的佐剂
- 批准号:
23K17212 - 财政年份:2023
- 资助金额:
$ 16.98万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Effects of Tobacco Heating System on the male reproductive function and towards to the reduce of the adverse effects.
烟草加热系统对男性生殖功能的影响以及减少不利影响。
- 批准号:
22H03519 - 财政年份:2022
- 资助金额:
$ 16.98万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Mitigating the Adverse Effects of Ultrafines in Pressure Filtration of Oil Sands Tailings
减轻油砂尾矿压力过滤中超细粉的不利影响
- 批准号:
563657-2021 - 财政年份:2022
- 资助金额:
$ 16.98万 - 项目类别:
Alliance Grants
1/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
1/4-破译ECT结果和不良反应的机制(DECODE)
- 批准号:
10521849 - 财政年份:2022
- 资助金额:
$ 16.98万 - 项目类别:
4/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
4/4-破译ECT结果和不良反应的机制(DECODE)
- 批准号:
10671022 - 财政年份:2022
- 资助金额:
$ 16.98万 - 项目类别:
2/4 Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
2/4 ECT 结果和不良反应的破译机制(DECODE)
- 批准号:
10670918 - 财政年份:2022
- 资助金额:
$ 16.98万 - 项目类别:
Adverse Effects of Using Laser Diagnostics in High-Speed Compressible Flows
在高速可压缩流中使用激光诊断的不利影响
- 批准号:
RGPIN-2018-04753 - 财政年份:2022
- 资助金额:
$ 16.98万 - 项目类别:
Discovery Grants Program - Individual