In Vitro Evaluation of a Device for Intra-Pulmonary Aerosol Generation and Delivery

Abstract

For infants born with respiratory distress syndrome (RDS), liquid bolus delivery of surfactant administered through an endotracheal tube is common practice. While this method is generally effective, complications such as transient hypoxia, hypercapnia, and altered cerebral blood flow may occur. Aerosolized surfactant therapy has been explored as an alternative. Unfortunately, past efforts have led to disappointing results as aerosols were generated outside the lungs with significant pharyngeal deposition and minimal intrapulmonary instillation. A novel aerosol generator (Microjet™) is evaluated herein for intrapulmonary aerosol generation within an endotracheal tube and tested with Curosurf and Infasurf surfactants. Compared with other aerosol delivery devices, this process utilizes low air flow (range 0.01–0.2 L min⁻¹) that is ideal for limiting potential barotrauma to the premature newborn lung. The mass mean diameter (MMD) of the particles for both tested surfactants was less than 4 μm, which is ideal for both uniform and distal lung delivery. As an indicator of phospholipid function, surfactant surface tension was measured before and after aerosol formation—with no significant difference. Moreover, this device has an outside diameter of <1 mm, which permits insertion into an endotracheal tube (of even 2.0 mm). In the premature infant where intravenous access is either technically challenging or difficult, aerosol drug delivery may provide an alternative route in patient resuscitation, stabilization, and care. Other potential applications of this type of device include the delivery of nutrients, antibiotics, and analgesics via the pulmonary route.

Copyright 2015 American Association for Aerosol Research

ACKNOWLEDGMENTS

The authors would like to thank the University of Minnesota Fairview Children's Hospital pharmacy for providing Curosurf and Infasurf and Zehraa Cheaib with manuscript assistance.

FUNDING

Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114 and NIH SBIR 5R44EY016229-05. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health.

DISCLOSURE STATEMENT

Dr. Zeeshan Syedain was affiliated with Powerscope Inc. and the University of Minnesota at the time of this research. Dr. Amir Naqwi had ownership in Powerscope Inc. Drs. Myrna Dolovich and Arif Somani have no financial support from Powerscope. Dr. Somani has a collaborative grant submitted (R43 Sept. 2013) with MSP Corp.