In Vitro Evaluation of High Flow Gas and Aerosol Drug Delivery Using Anatomically Biorelevant Infant and Child Airway Replicas
Doctor of Philosophy
Mechanical and Nuclear Engineering
Respiratory care has greatly evolved from the use of an iron lung to treat patients with polio to now having at home continuous positive airway pressure (CPAP) machines for sleep apnea. Additionally, advances have been made in drug delivery as common delivery methods, such as spray and nebulizer devices, are used extensively for treatment of various pulmonary diseases and in some cases even used to deliver vaccines. More recently, 3D printing has allowed for anatomically-accurate physical airway models to be developed to better understand the countless number of therapies involving regional aerosol deposition as well as physical effects of therapies such as CPAP. The use of in vitro airway replicas is especially beneficial for younger populations considering the lack of, or inability to perform, extensive clinical studies on infants and children. As such, these models are able to provide a more comprehensive evaluation of different therapies and determine their effectiveness, without sacrificing realistic conditions.
Aim 1 of this study was to use anatomically-similar in vitro replicas of nasal airways of five infants (3- to 24-months-old) to evaluate the regional deposition of a model vaccine formulation and determine the efficiency of four potential intranasal delivery devices under a bi-dose delivery method. Administration parameters of the devices, including insertion depth and administration angles were measured, but were not directly controlled to mimic clinical settings. Overall, the deposition was found to be independent of the delivery method as it pertained to the time of administration within the breathing cycle for all devices, with limited exceptions. Additionally, each device was able to deliver a significant amount of formulation (over 80%) to the targeted regions of interest, while also minimizing delivery to undesirable areas (< 1%). Although, there were no practical differences found in the delivery efficiency of the devices with regards to the models, there were differences in regional deposition data in the different models.
Aim 2 looked to evaluate the pressure support delivered using high flow nasal cannula (HFNC) therapy in infants (3- to 24-months-old) and create predictive correlations accounting for subject and therapy specific parameters. Six in vitro nasal airway models were attached to an infant lung model, with pressure being evaluated in the nasopharynx and trachea. Airway pressures were measured with the infant lung model being capped and uncapped, in order to evaluate the full range of expected levels of pressure support, in addition to using a latex dental dam attached to the bottom of the lungs to simulate airway compliance. Flow was delivered using five commercially available cannulas, appropriately sized for the ages considered, as well as five custom designed cannulas. Influential factors affecting the pressure support were evaluated including the airway resistance, airway compliance, supplied flow rate, and cannula dimensions, such as inner diameter and occlusion ratio. The pressure support was accurately captured in the nasopharynx and trachea using the mechanical energy balance, incorporating the therapy specific parameters, with further improvement found by incorporating the airway resistance.
Aim 3 focused on evaluating previously developed oral airway deposition in children (6- to 14-years) and determine if the predictive correlation was able to accurately predict the deposition when utilizing alternative carrier gases. The same in vitro models that were used to develop the original deposition correlation were used to evaluate the correlation for air and a helium-oxygen mixture, commonly referred to as heliox, under realistic breathing conditions. Overall, aerosol deposition for both carrier gases were found to be accurately captured among the population of models; however, the correlation was not able to accurately predict the deposition on an individual basis. On an individual basis, the correlation was more accurate in predicting the deposition with air as the carrier gas, but was not able to capture the deposition when using heliox.
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Available for download on Wednesday, August 12, 2026