A path forward in the development of new aerosol drug delivery devices for pediatrics

Inhaled medications are widely accepted as being the optimal route for treating pediatric respiratory diseases, a leading cause of hospitalization and death. Despite jet nebulizers being the preferred inhalation device for neonates and infants, current devices face performance issues with most of the drug never reaching the target lung location. Previous work has aimed to improve pulmonary drug deposition, yet nebulizer efficiency remains low. The development of an inhalant therapy that is efficacious and safe for pediatrics depends on a well-designed delivery system and formulation. To accomplish this, the field needs to rethink the current practice of basing pediatric treatments on adult studies. The rapidly evolving pediatric patient (i.e. neonates to eighteen) needs to be considered because they are different from adults with respect to airway anatomy, breathing patterns, and adherence. Previous research approaches to improve deposition efficiency have been limited due to the complexity of combining physics, which drives aerosol transport and deposition, and biology, especially within the area of pediatrics. To address these critical knowledge gaps, we need a better understanding of how patient age and disease state affect deposition of aerosolized drugs. The complexity of the multiscale respiratory system makes scientific investigation very challenging. The authors have simplified the complex problem into five components with these three areas as ones to address first: how the aerosol is (i) generated in a medical device, (ii) delivered to the patient, and (iii) deposited inside the lung. In this review, we discuss the technological advances and innovations made from experiments, simulations, and predictive models in each of these areas. In addition, we discuss the impact on patient treatment efficacy and recommend a clinical direction, with a focus on pediatrics. In each area, a series of research questions are posed and steps for future research to improve efficacy in aerosol drug delivery are outlined.