Aerosol: A Novel Vehicle for Pharmacotherapy in Neonates

BACKGROUND:Local delivery of drugs to the lungs of newborn infant represents an unmet need as no drugs have been approved. Potential benefits could be large. Development of aerosol for delivery of drugs to infants and newborn offers huge potential for better therapy. Newborn infants present unique challenges with regard to aerosol therapy. Efficient deposition of aerosolized medications on the neonate airway surface is hampered by anatomical features such as small airway geometries and physiological features such as exquisitely small tidal volumes, rapid breathing and unfavorable inhalation:exhalation ratios. METHODS:The selection of aerosol generators capable of delivering any more than a few percent of the nominal drug dose to the airways remains extremely limited with nebulizers and pressurized metered dose inhalers being predominantly used. Further hampering the development of bespoke high performance aerosol therapy for neonates is the as yet unknown ideal droplet size. RESULTS:Droplet size is a critical determinant of the amount of aerosol that escapes the patient circuit, becoming available to the patient, and subsequently the location of deposition within the lung. It is assumed that smaller is better at traversing the tortuous path from aerosol generator to airway surface. To date, patient interface has been shown to have little effect with respect to delivered dose, but some may provide advantage with respect to ease of use and patient acceptance. CONCLUSION:The present review iteratively describes the difficulties in achieving optimized aerosol drug delivery in neonates. We suggest possible technical solutions aimed at improving delivery and developing a platform for increased reliability and reproducibility of dosing such that new and existing medications may exploit the potential advantages of aerosol therapy in the neonate population.