Devices and Methods for the Efficient Delivery of Surfactant Aerosol Therapy to the Lungs of Infants
Author ORCID Identifier
https://orcid.org/0000-0003-2443-5570
Defense Date
2025
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Mechanical and Nuclear Engineering
First Advisor
Dr. Worth Longest
Second Advisor
Dr. Michael Hindle
Third Advisor
Dr. Daren Chen
Fourth Advisor
Dr. Laleh Golshahi
Fifth Advisor
Dr. Rebecca Heise
Abstract
This research project focuses on non- and minimally-invasive pharmaceutical aerosol systems for low- to high-income countries that improve the delivery of dry powder aerosols to the lungs of neonates with an emphasis on surfactant aerosol therapies to treat respiratory distress syndrome (RDS), a significant advancement compared with the current approach of high-risk intubation and lung instillation of high-volume liquid boluses. Several key components and strategies have been combined to achieve this goal: (1) state-of-the-art infant air-jet dry powder inhaler (DPI) technology, (2) engineered spray-dried powder formulations, (3) an excipient enhanced growth (EEG) strategy for regional dose targeting and efficient upper airway transmission, (4) advances in patient interface design, and (5) in vitro methods (such as airway pressure modeling using simulation of pulmonary mechanics (PM), quantification of regional deposition, and aerosol size characterization) to ensure realistic testing conditions and elucidate critical transport dynamics. The first objective required development of the infant air-jet DPI aerosol delivery system (iDP-ADS), which uses a direct-to-infant (D2I) strategy, with a bifurcating dual-prong nasal interface for the administration of a model spray-dried albuterol EEG formulation. Using a co-flow approach with a flexible ergonomic prong design, lung delivery efficiencies of 34% and 45% (based on loaded dose; compared to 0 – 14% with other systems) were achieved in full-term and 34-week gestational age (GA) preterm infant airway models, respectively, with age-appropriate resistance and compliance while maintaining targeted positive end-expiratory pressure (PEEP) between 4 – 6 cm H2O and peak inspiratory pressures (PIPs) below 25 cm H2O. Furthermore, the hygroscopic growth of a novel synthetic lung surfactant EEG (SLS-EEG) powder formulation was assessed using physiologically-realistic thermodynamic conditions, revealing a diameter growth ratio of 1.7 (and mass increase ratio of 5-fold) following particle residence times consistent with a breath cycle and final aerosol mass median aerodynamic diameter of 3.11 µm for enhanced alveolar retention. The second objective resulted in a first-of-its-kind laryngeal mask airway ADS (LMA-ADS) capable of delivering ~22% and ~29% (based on device-loaded dose) of an SLS-EEG powder to the tracheal filter of a preterm infant nose-throat in vitro model with and without PM, respectively, after the development and optimization of a co-flow design. The third objective integrated bubble CPAP into the LMA-ADS for different levels of pressure support: termed open and full pressure assistance. Both configurations, regardless of the level of PEEP, air source (an electromechanical timer for high-resourced settings or a hand actuator for low- and middle-income countries), use of a breath-hold, or device/mass loading combination, produced similar aerosol transmission (~20%) during timing of device actuation with the beginning of inhalation and demonstrated safe operating parameters. In summary, this work contributes multiple platforms for rapid and efficient administration of dry powder surfactant aerosols to the lungs of premature infants in combination with providing critical respiratory ventilation support that maintains lung pressures within targeted ranges.
Rights
© Sarah C. Strickler
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
12-11-2025