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

基本信息

批准号：
7760144
负责人：
P. Worth Longest
金额：
$ 18.24万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-01-10 至 2011-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7760144
关键词：
Adverse effects Aerosols Air Air Conditioning Albuterol Albuterol Sulfate Animals Benign Breathing Bronchi Computer Simulation Coupling Cromolyn Sodium Cystic Fibrosis Data Deposition Development Devices Diabetes Mellitus Distal Dose Drug Delivery Systems Effectiveness Elements Environment Evaluation Exhalation Future Gases Generations Goals Growth Guidelines Heating Housing Human Humidifier Humidity In Vitro Insulin Isotonic Exercise Joints Liquid substance Lung Lung diseases Malignant neoplasm of lung Measures Medical Medicine Methods Modeling Oral cavity Outcome Pharmaceutical Preparations Pharmacologic Substance Pharyngeal structure Phase Physical condensation Property Proteins Relative (related person)Reporting Research Respiratory System Respiratory Tract Infections Respiratory tract structure Sample Size Simulate Solid Solutions Source Specific qualifier value System Techniques Temperature Testing Therapeutic Tracheobronchial Upper respiratory tract Validation Water aqueous base chronic pain conditioning density design improved in vitro Model in vivo insight interest nanoparticle new technology next generation novel particle physical property public health relevance research study respiratory therapy development water solution water vapor

项目摘要

DESCRIPTION (provided by applicant): Inhaled pharmaceutical aerosols are often deposited in the lung at very low deposition efficiencies. Perhaps more significant than the quantity of drug deposited is the large inter- and intra-subject variability that is often observed with these medicinal aerosols and the associated dose delivered to the lung. In order to make many next-generation inhaled medications a viable drug delivery alternative, increased lung delivery and decreased inter- and intra-subject variability are of critical importance. The objective of this study is to develop an approach for improved lung delivery and retention of nanoparticle and submicrometer aerosols using enhanced condensation growth. This concept consists of combining (1) a controlled inhalable water vapor humidity source with (2) a submicrometer aerosol generation and delivery device. The humidity source is used to create a controlled supersaturated relative humidity environment within general regions of the lung. This conditioning of the respiratory tract may be accomplished through an inhalation of supersaturated water vapor with pre-specified temperature and relative humidity (RH) conditions. The aerosol, in particle or droplet form, will be delivered either concurrently or following the controlled inhalation of the humidity source. The aerosol should have a size that can effectively penetrate the mouth-throat and upper tracheobronchial regions, e.g., approximately 1 ¿m and below. Upon transport into the lung, the aerosol will increase in size due to enhanced condensation growth (water accumulation) in the controlled supersaturated environment, thereby increasing retention. To achieve this objective, the following specific aims are proposed: Specific Aim 1: Develop an in vitro system to evaluate the controlled enhanced condensation growth concept in the upper respiratory tract and assess the effects of RH under steady flow conditions. Specific Aim 2: Develop and validate a computational fluid dynamics (CFD) model of hygroscopic droplet growth in the upper tracheobronchial region and apply the model to evaluate aqueous wall boundary conditions and transport into distal bronchi. Specific Aim 3: Employ the developed in vitro and CFD models to test the effects of (1) transient flow, (2) aerosol concentration density, and (3) aerosol hygroscopic properties and physical form on the hygroscopic growth of 100 - 1000 nm aerosols. By delivering submicrometer aerosols past the mouth-throat and then increasing aerosol size through enhanced condensation growth, significant reductions in upper airway deposition and increased lung retention are expected. As a result, reduced variability in dose can be achieved, which is necessary for the effective use of many next-generation pharmaceutical aerosols. Public Health Relevance: A number of inhalable medications are in development for the treatment of respiratory diseases (such as lung cancer, respiratory infections, and cystic fibrosis) and systemic conditions (such as diabetes, chronic pain, and growth deficiency). However, the delivery of these next- generation inhaled pharmaceuticals to the lungs is often inefficient, which can significantly reduce drug effectiveness and increases unwanted side effects. The overall goal of this project is to develop a novel technology for the efficient delivery of inhaled medicines that minimizes deposition in the mouth and throat and maximizes deposition in the lungs.

描述（由申请人提供）：吸入的药物气雾剂通常以非常低的沉积效率沉积在肺部，也许比沉积的药物量更重要的是经常在这些药物气雾剂和药物中观察到的巨大的受试者间和受试者内变异性。为了使许多下一代吸入药物成为可行的药物输送替代方案，增加肺部输送和减少受试者间和受试者内的变异性至关重要。这项研究的目的是开发一种利用增强的冷凝生长来改善纳米颗粒和亚微米气溶胶的肺部输送和保留的方法，该概念包括将 (1) 受控可吸入水蒸气湿度源与 (2) 亚微米气溶胶生成和输送装置相结合。湿度源用于在肺部的一般区域内创建受控的过饱和相对湿度环境，可以通过吸入具有预先指定的温度和相对湿度的过饱和水蒸气来实现。 (RH) 条件下，颗粒或液滴形式的气雾剂将在受控吸入湿度源的同时或之后进行输送。气雾剂的尺寸应能够有效地穿透口腔和气管支气管上部区域。大约 1 ¿米及以下的气溶胶在受控过饱和环境中由于冷凝增长（水积累）而增大，从而增加滞留量。为了实现这一目标，提出了以下具体目标：具体目标 1。：开发一个体外系统来评估上呼吸道的受控增强凝结生长概念，并评估 RH 在稳定流动条件下的影响。具体目标 2：开发并验证计算流体动力学 (CFD) 模型。具体目标 3：采用开发的体外和 CFD 模型来测试 (1) 瞬态流、(2) 的影响。气溶胶浓度密度，以及 (3) 气溶胶吸湿特性和物理形态对 100 - 1000 nm 气溶胶吸湿生长的影响。亚微米气溶胶通过口腔，然后通过增强凝结生长来增加气溶胶尺寸，预计会显着减少上呼吸道沉积并增加肺滞留，从而减少剂量的变化，这对于有效使用亚微米气溶胶是必要的。许多下一代药物气雾剂。公共卫生相关性：许多吸入药物正在开发中，用于治疗呼吸道疾病（例如肺癌、呼吸道感染和囊性纤维化）和全身性疾病（例如糖尿病、慢性疼痛和生长缺陷）。将这些下一代吸入药物输送到肺部通常效率低下，这会显着降低药物有效性并增加不必要的副作用。该项目的总体目标是开发一种有效输送吸入药物的新技术，最大限度地减少肺部沉积。这口腔和喉咙，并最大限度地沉积在肺部。