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.

Public Health Relevance

Patients receiving non-invasive ventilation (NIV) for respiratory support frequently need pharmaceutical aerosols to treat conditions like asthma, COPD, pulmonary hypertension, lung infections, and cystic fibrosis. However, 90% or more of the drug never reaches the patient's lungs due to deposition and loss in the NIV delivery system and nasal airways, which wastes potentially expensive medication and increases side effects. The overall goal of this project is to develop a novel technology for the efficient delivery of pharmaceutical aerosols during NIV that minimizes depositional losses in the delivery system and nasal airways and maximizes drug delivery to the lungs.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL107333-03
Application #
8445248
Study Section
Gene and Drug Delivery Systems Study Section (GDD)
Program Officer
Punturieri, Antonello
Project Start
2011-06-01
Project End
2015-11-30
Budget Start
2013-11-01
Budget End
2014-11-30
Support Year
3
Fiscal Year
2014
Total Cost
$397,359
Indirect Cost
$122,199
Name
Virginia Commonwealth University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298
Behara, Srinivas R B; Longest, P Worth; Farkas, Dale R et al. (2014) Development of high efficiency ventilation bag actuated dry powder inhalers. Int J Pharm 465:52-62
Tian, Geng; Hindle, Michael; Longest, P Worth (2014) Targeted Lung Delivery of Nasally Administered Aerosols. Aerosol Sci Technol 48:434-449
Behara, Srinivas R B; Farkas, Dale R; Hindle, Michael et al. (2014) Development of a high efficiency dry powder inhaler: effects of capsule chamber design and inhaler surface modifications. Pharm Res 31:360-72
Walenga, Ross L; Tian, Geng; Hindle, Michael et al. (2014) Variability in Nose-to-Lung Aerosol Delivery. J Aerosol Sci 78:11-29
Behara, Srinivas R B; Longest, P Worth; Farkas, Dale R et al. (2014) Development and comparison of new high-efficiency dry powder inhalers for carrier-free formulations. J Pharm Sci 103:465-77
Longest, P Worth; Azimi, Mandana; Golshahi, Laleh et al. (2014) Improving aerosol drug delivery during invasive mechanical ventilation with redesigned components. Respir Care 59:686-98
Son, Yoen-Ju; Longest, P Worth; Tian, Geng et al. (2013) Evaluation and modification of commercial dry powder inhalers for the aerosolization of a submicrometer excipient enhanced growth (EEG) formulation. Eur J Pharm Sci 49:390-9
Son, Yoen-Ju; Worth Longest, P; Hindle, Michael (2013) Aerosolization characteristics of dry powder inhaler formulations for the excipient enhanced growth (EEG) application: effect of spray drying process conditions on aerosol performance. Int J Pharm 443:137-45
Golshahi, Laleh; Tian, Geng; Azimi, Mandana et al. (2013) The use of condensational growth methods for efficient drug delivery to the lungs during noninvasive ventilation high flow therapy. Pharm Res 30:2917-30
Longest, P Worth; Walenga, Ross L; Son, Yoen-Ju et al. (2013) High-efficiency generation and delivery of aerosols through nasal cannula during noninvasive ventilation. J Aerosol Med Pulm Drug Deliv 26:266-79

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