Improving the Lung Delivery of Nasally Administered Aerosols During Noninvasive Ventilation-An Application of Enhanced Condensational Growth (ECG)

Background: Aerosol drug delivery during noninvasive ventilation (NIV) is known to be inefficient due to high depositional losses. To improve drug delivery efficiency, the concept of enhanced condensational growth (ECG) was recently proposed in which a submicrometer or nanoaerosol reduces extrathoracic deposition and subsequent droplet size increase promotes lung retention. The objective of this study was to provide proof-of-concept that the ECG approach could improve lung delivery of nasally administered aerosols under conditions consistent with NIV. Methods: Aerosol deposition and size increase were evaluated in an adult nose-mouth-throat (NMT) replica geometry using both in vitro experiments and CFD simulations. For the ECG delivery approach, separate streams of a submicrometer aerosol and warm (39 degrees C) saturated air were generated and delivered to the right and left nostril inlets, respectively. A control case was also considered in which an aerosol with a mass median aerodynamic diameter (MMAD) of 4.67 mu m was delivered to the model. Results: In vitro experiments showed that the ECG approach significantly reduced the drug deposition fraction in the NMT geometry compared with the control case [14.8 (1.83)%-ECG vs. 72.6 (3.7)%-control]. Aerosol size increased from an initial MMAD of 900nm to a size of approximately 2 mu m at the exit of the NMT geometry. Results of the CFD model were generally in good agreement with the experimental findings. Based on CFD predictions, increasing the delivery temperature of the aerosol stream from 21 to 35 degrees C under ECG conditions further reduced the total NMT drug deposition to 5% and maintained aerosol growth by ECG to approximately 2 mu m. Conclusions: Application of the ECG approach may significantly improve the delivery of pharmaceutical aerosols during NIV and may open the door for using the nasal route to routinely deliver pulmonary medications.