Aerosol drug delivery to spontaneously-breathing preterm neonates: lessons learned

Delivery of medications to preterm neonates receiving non-invasive ventilation (NIV) represents one of the most challenging scenarios for aerosol medicine. This challenge is highlighted by the undersized anatomy and the complex (patho)physiological characteristics of the lungs in such infants. Key physiological restraints include low lung volumes, low compliance, and irregular respiratory rates, which significantly reduce lung deposition. Such factors are inherent to premature birth and thus can be regarded to as the intrinsic factors that affect lung deposition. However, there are a number of extrinsic factors that also impact lung deposition: such factors include the choice of aerosol generator and its configuration within the ventilation circuit, the drug formulation, the aerosol particle size distribution, the choice of NIV type, and the patient interface between the delivery system and the patient. Together, these extrinsic factors provide an opportunity to optimize the lung deposition of therapeutic aerosols and, ultimately, the efficacy of the therapy.In this review, we first provide a comprehensive characterization of both the intrinsic and extrinsic factors affecting lung deposition in premature infants, followed by a revision of the clinical attempts to deliver therapeutic aerosols to premature neonates during NIV, which are almost exclusively related to the non-invasive delivery of surfactant aerosols. In this review, we provide clues to the interpretation of existing experimental and clinical data on neonatal aerosol delivery and we also describe a frame of measurable variables and available tools, including in vitro and in vivo models, that should be considered when developing a drug for inhalation in this important but under-served patient population.

Automated summary

The delivery of medications to preterm neonates receiving non-invasive ventilation (NIV) is a challenging scenario for aerosol medicine due to anatomical and physiological characteristics of the lungs in such infants. Factors such as low lung volumes, compliance, and irregular respiratory rates affect lung deposition. Extrinsic factors like aerosol generator choice, drug formulation, particle size distribution, NIV type, and patient interface also impact lung deposition and offer an opportunity to optimize therapy efficacy. Existing experimental and clinical data on neonatal aerosol delivery are examined, with a focus on non-invasive delivery of surfactant aerosols, providing insights and a framework for the development of inhaled drugs in this patient population.