Children comprise roughly 27% of the world’s population, yet pediatric trials make up 17% of the total number of clinical trials registered with the World Health Organization, with only 7% of trials taking place in newborns. Approved adult therapeutics are often used off-label for children, and can take up to 7 years longer to go from the first clinical trial in adults to the first trial in children. These numbers highlight a significant gap in technology development for the neonatal and pediatric populations, particularly technology that focuses on improving therapeutic outcomes for children and newborns with a range of conditions. Our research seeks to develop and evaluate therapeutic delivery systems for newborns and children, whom have unique physiologies compared to adults. We have a specific focus on engineering therapeutics that mitigate or attenuate ongoing injury in the brain, with the goal to improve neurological function and quality of life across the lifespan. In this talk, we will discuss our use of whole hemisphere brain slices to screen therapeutics, including nanotherapeutics. We will show key design considerations that increase nanoparticle uptake and transport within the brain for improved neuroprotection in neonatal and pediatric brain diseases. We will close with a forward-thinking perspective on how we can improve translation of drug delivery technologies to the clinic for neonatal and pediatric populations.