Effective Delivery of Pharmaceutical Aerosols during Non-Invasive Ventilation

无创通气期间药物气雾剂的有效输送

• 批准号: 8445248
• 负责人: Michael Hindle
• 金额: $ 43.27万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8445248
• 关键词: Acute; Address; Adult; Adverse effects; Aerosol Drug Therapy; Aerosols; Age; Air; Asthma; Breathing; Cannulas; Characteristics; Chest; Child; Chronic; Chronic Obstructive Airway Disease; Clinical; Computer Simulation; Critical Care; Custom; Cystic Fibrosis; Deposition; Development; Devices; Dose; Drug Combinations; Drug Delivery Systems; Environmental air flow; Excipients; Exhalation; Fostering; Generations; Geometry; Goals; Growth; Heating; Humidity; In Vitro; Infection; Inhalation Therapy; Intratracheal Intubation; Liquid substance; Lung; Masks; Mechanical ventilation; Medical; Methodology; Methods; Modeling; Nebulizer; Nose; Obstructive Lung Diseases; Outcome; Oxygen; Particle Size; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Pulmonary Hypertension; Respiratory Failure; Respiratory Insufficiency; Sleep Apnea Syndromes; Source; System; Techniques; base; experience; face mask; improved; new technology; next generation; novel; particle; patient home care; pressure; research study; respiratory; standard care; tool; wasting

DESCRIPTION (provided by applicant): Non-invasive ventilation (NIV) is currently a form of standard care for patients suffering from respiratory insufficiency, sleep apnea, chronic obstructive pulmonary disease (COPD) and more severe acute and chronic respiratory failure. Patients receiving NIV typically have underlying respiratory and systemic conditions that can be effectively treated with pharmaceutical aerosols. Administration of aerosol therapy simultaneously with NIV allows for continuous ventilation support. However, drug delivery efficiency to patients during NIV is very low (1-7% of the initial dose), resulting in high dose variability, increased side effects, and wasted medication. The objective of this study is to develop aerosol drug delivery systems that can significantly improve pulmonary drug deposition during NIV using a condensational growth approach. Three non-invasive ventilation techniques will be considered: (1) high-flow therapy (HFT) with heat and humidity using a cannula interface, (2) oxygen low-flow therapy (LFT) through a nasal cannula, and (3) non-invasive positive pressure ventilation (NPPV) through a face mask. The condensational growth concept begins with generating and delivering initially submicrometer aerosols (100 - 900 nm) to minimize deposition and loss in the delivery lines, patient interface, and extra thoracic airways. The aerosol is delivered with a saturated or supersaturated warm airstream and/or with the inclusion of hygroscopic excipients in order to foster condensational growth, leading to increased aerosol size and pulmonary deposition. Specifically, enhanced condensational growth (ECG) is achieved by combining the aerosol with a humidified airstream at the entrance to or within the airways, while enhanced excipient growth (EEG) consists of delivering combination drug and hygroscopic excipient submicrometer particles. Development and optimization of the aerosol delivery systems will be based on concurrent in vitro experiments and computational simulations in realistic models of the extra thoracic airways. In order to develop this novel respiratory drug delivery strategy, the following specific aims are proposed. Specific Aim 1: Develop an effective respiratory drug delivery system for use during nasal HFT based on enhanced condensational growth (ECG). Specific Aim 2: Develop an effective respiratory drug delivery technique for use with a low-flow nasal cannula oxygen system based on enhanced excipient growth (EEG). Specific Aim 3: Develop an effective respiratory drug delivery methodology for use with NPPV based on a combination of ECG and EEG. By delivering a submicrometer aerosol through the NIV system and extra thoracic nasal airways, and then increasing aerosol size with condensational growth, significant reductions in depositional losses are expected. As a result of using this concept, reduced variability in dose can be achieved together with near full lung retention, which is necessary for the effective use of many current and next-generation medical aerosols.

描述（由申请人提供）：无创通气（NIV）目前是一种标准护理形式，适用于患有呼吸功能不全、睡眠呼吸暂停、慢性阻塞性肺病（COPD）以及更严重的急慢性呼吸衰竭的患者。接受 NIV 的患者通常患有潜在的呼吸系统和全身疾病，可以使用药物气雾剂进行有效治疗。气雾疗法与 NIV 同时给药可提供持续通气支持。然而，NIV 期间向患者的药物输送效率非常低（初始剂量的 1-7%），导致剂量变异性大、副作用增加和药物浪费。本研究的目的是开发气雾剂药物输送系统，该系统可以使用冷凝生长方法显着改善 NIV 期间的肺部药物沉积。将考虑三种无创通气技术：（1）使用插管接口进行热湿高流量治疗（HFT），（2）通过鼻插管进行氧气低流量治疗（LFT），以及（3）非侵入性通气治疗。 - 通过面罩进行有创正压通气 (NPPV)。冷凝生长概念首先产生并输送亚微米气溶胶（100 - 900 nm），以最大限度地减少输送管线、患者界面和胸腔外气道中的沉积和损失。气雾剂通过饱和或过饱和的暖气流和/或包含吸湿性赋形剂来输送，以促进凝结生长，导致气雾剂尺寸增加和肺部沉积。具体来说，增强冷凝生长（ECG）是通过在气道入口处或气道内将气雾剂与加湿气流结合来实现的，而增强赋形剂生长（EEG）则包括递送组合药物和吸湿性赋形剂亚微米颗粒。气雾剂输送系统的开发和优化将基于同时进行的体外实验和胸外气道真实模型的计算模拟。为了开发这种新型呼吸药物输送策略，提出了以下具体目标。具体目标 1：开发一种有效的呼吸药物输送系统，用于基于增强凝结生长 (ECG) 的经鼻 HFT。具体目标 2：开发一种有效的呼吸药物输送技术，用于基于增强赋形剂生长 (EEG) 的低流量鼻插管氧气系统。具体目标 3：结合心电图和脑电图，开发一种有效的呼吸药物输送方法，用于 NPPV。通过 NIV 系统和胸外鼻气道输送亚微米气溶胶，然后通过凝结生长增加气溶胶尺寸，预计可显着减少沉积损失。使用这一概念的结果是，可以实现剂量变异性的减少以及几乎完全的肺滞留，这对于有效使用许多当前和下一代医用气雾剂是必要的。