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: 8269658
• 负责人: Michael Hindle
• 金额: $ 46.65万
• 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 2015-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8269658
• 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; 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）：非侵入性通气（NIV）目前是一种标准护理的一种形式，适用于患有呼吸道不足，睡眠呼吸暂停，慢性阻塞性肺疾病（COPD）以及更严重的急性和慢性呼吸衰竭的患者。接受NIV的患者通常具有潜在的呼吸和全身性疾病，可以通过药物气溶胶有效治疗。与NIV同时使用气溶胶治疗可以进行连续的通风支持。但是，NIV期间患者的药物递送效率非常低（占初始剂量的1-7％），导致高剂量变异性，增加副作用和浪费药物。这项研究的目的是开发可使用冷凝生长方法在NIV期间显着改善肺部药物沉积的气溶胶药物输送系统。将考虑三种非侵入性通风技术：（1）使用套管界面使用热量和湿度的高流量治疗（HFT），（2）（2）氧气低流量治疗（LFT）通过鼻套管，（3）非侵入性阳性压力通气（NPPV）通过面膜。冷凝生长概念始于产生和交付最初的亚微米气溶胶（100-900 nm），以最大程度地减少递送线，患者界面和额外胸腔气道的沉积和损失。气溶胶采用饱和或过饱和的温暖气流和/或含有吸湿性赋形剂以促进冷凝水的生长，从而导致气溶胶大小和肺部沉积增加。具体而言，通过将气溶胶与气道在气道入口或气道内的加湿气流相结合而实现增强的凝聚力生长（ECG），而增强的摄取剂生长（EEG）则包括提供组合药物和吸湿性赋形剂亚微米颗粒。气溶胶递送系统的开发和优化将基于同时进行的体外实验和计算模拟，在额外的胸通气的现实模型中。为了制定这种新颖的呼吸药输送策略，提出了以下特定目标。具体目标1：基于增强的冷凝剂生长（ECG），开发有效的呼吸道药物输送系统，以便在鼻HFT期间使用。特定目标2：开发一种有效的呼吸药输送技术，用于基于增强赋形剂生长（EEG）的低流量鼻套管氧气系统。特定目的3：基于ECG和EEG的组合，开发有效的呼吸药输送方法，以与NPPV一起使用。通过通过NIV系统和额外的胸腔气道传递亚微米气溶胶，然后随着冷凝水的生长增加气溶胶的大小，预计沉积损失会大大减少。通过使用此概念，可以与几乎全肺保留率一起实现剂量的降低，这对于有效使用许多当前和下一代医疗气溶胶是必不可少的。