This video illustrates an Infant Air-Jet DPI with a variable aerosolization chamber for the rapid administration of high-dose dry powder aerosol to infants.  A 30 mg dose of synthetic lung surfactant (SLS-) excipient enhanced growth (EEG) powder formulation is initially loaded into the aerosolization chamber.  Total device preparation time is ~20 sec.  The device is then actuated to form an aerosol with 10 mL boluses of air.  Rotation of the lower unit through levels 1-4 raises the floor of of the aerosolization chamber and presents a new consistent dose for aerosol formation during the next actuation.  Using this process, the 30 mg loaded dose can be fully delivered in 4 actuations with a highly consistent mass per actuation and a highly uniform small-particle aerosol size in the range of 1.4-1.5 micrometers (volumetric median diameter) across all actuations.  Total delivery time for the 30 mg dose is 20 sec.

This video illustrates our infant aerosol delivery system for administering surfactant aerosols using the nose-to-lung route.  As developed in Howe et al. (2021), the device consists of an air-jet dry powder inhaler (DPI) and gradually expanding nasal cannula with a single prong interface.  In this video a realistic in vitro nasal airway model of a full-term infant is implemented with a tracheal filter to estimate the lung delivered dose of aerosol. A custom auto-actuator has been added that delivers variable air volumes and pressures depending on the infant's weight and lung condition.  In this study, an air volume of 30 ml for a full-term infant was used to deliver the aerosol and provide a full inhalation breath.  After depressing the auto-actuator trigger, a 5 second breath-hold is used to help the aerosol deposit within the lungs and targeted alveolar airways.  The infant's other nostril is then released to allow for exhalation and additional administration cycles are implemented to empty the surfactant powder from the device.  Using a highly dispersible spray-dried excipient enhanced growth powder formulation, the system currently delivers approximately 50% of the loaded dose to the lungs of the full-term infant model.  Additional system improvements and optimizations are ongoing along with testing in preterm infant models.

This video illustrates the flow field created by a common dry powder inhaler (DPI) within the mouth-throat geometry based on computational fluid dynamics (CFD) simulations.  The Flovent Diskus DPI (GlaxoSmithKline, Raleigh, NC) was evaluated, which delivered a 250 mcg dose of fluticasone propionate in the form of a micronized powder attached to larger lactose carrier particles.  The patient inhales quickly-and-deeply (QD) through the device consistent with current instructions for correct DPI use.  A turbulent jet of high velocity air is generated within the device to break apart the powder and form an aerosol that is small enough for inhalation.  However, the video illustrates that the high velocity jet enters the mouth-throat and has a significant impact on the transport of the aerosol.  The jet initially impinges on the back of the throat providing a site of likely aerosol depositional loss. Interactions with the tongue create a low pressure region which also pulls the jet down (Coanda effect).  As with the MDI, the flow physics of the DPI system are highly complex and include transient flow, high levels of turbulence, and compressible flow in the two small jets on either side of the central jet.  Vortex shedding in these systems is common, often affecting the particle deposition profiles.  Simulations of the associated particle phase result in ~70% mouth-throat depositional loss of the aerosol, arising from impaction and turbulent dispersion.  These predictions were in very good agreement with concurrent in vitro deposition results using an identical system as described by Tian et al. (2011).  

This video illustrates particle transport and deposition for aerosols delivered from a common MDI (Flovent HFA) and DPI (Flovent Diskus).  As described by Longest et al. (2012), correct inhalation profiles of slow-and-deep (SD) and quick-and-deep (QD) waveforms are employed with the MDI and DPI, respectively.  For the MDI, a burst of spray momentum is observed to result in rapid deposition throughout the oral cavity followed by relatively slow inhalation for the remaining aerosol.  For the DPI, larger recirculation flow in the oral cavity and impaction result in significant depositional losses.  Deposition of the aerosol in the glottis is also observed for both cases.  Using these simulations, the study of Longest et al. (2012) illustrated that for the inhalers selected, the MDI was less sensitive to errors in the inhalation waveform.  Differences in regional lung deposition between the MDI and DPI were also illustrated, and they have important implications in device selection for treating different respiratory conditions. 

A targeted drug delivery technique that we have developed at VCU is referred to as the excipient enhanced growth (EEG) approach.  In this method, submicrometer particles are composed of an active medication and hygroscopic excipient to form the aerosol. The initial small size of the aerosol particles allows for low loss in the delivery system with effective deep lung delivery, and the inclusion of the hygroscopic excipient results in aerosol size increase within the lungs and targeted deposition.  The video illustrates the use of EEG delivery to target inhaled insulin to the lower airways.  The inhaled particles have an initial diameter of 900 nm and are composed of insulin (therapeutic) and sodium chloride (hygroscopic excipient) at a mass fraction of 50:50.  The initial submicrometer particle easily traverses the mouth-throat and upper airways with negligible (<1%) depositional loss, as reported by Tian et al. (2013).  Due to hygroscopic growth, the aerosol exiting bifurcation B7 has a mass median aerodynamic diameter (MMAD) of 2.8 micrometers, and with continued growth the aerosol MMAD exiting the terminal bronchioles (B15) and entering the acinar (alveolar) region is 5.7 micrometers.  The EEG approach provided at least an order of magnitude reduction in mouth-throat depositional loss and was shown by Tian et al. (2013) and Tian et al. (2014) to increase dose delivery to the small tracheobronchial airways by a factor of 20-40 compared with conventional inhalers.