Drug delivery platforms for neonatal brain injury

Abstract

Hypoxic-ischemic encephalopathy (HIE), initiated by the interruption of oxygenated blood supply to the brain, is a leading cause of death and lifelong disability in newborns. The pathogenesis of HIE involves a complex interplay of excitotoxicity, inflammation, and oxidative stress that results in acute to long term brain damage and functional impairments. Therapeutic hypothermia is the only approved treatment for HIE but has limited effectiveness for moderate to severe brain damage; thus, pharmacological intervention is explored as an adjunct therapy to hypothermia to further promote recovery. However, the limited bioavailability and the side-effects of systemic administration are factors that hinder the use of the candidate pharmacological agents. To overcome these barriers, therapeutic molecules may be packaged into nanoscale constructs to enable their delivery. Yet, the application of nanotechnology in infants is not well examined, and the neonatal brain presents unique challenges. Novel drug delivery platforms have the potential to magnify therapeutic effects in the damaged brain, mitigate side-effects associated with high systemic doses, and evade mechanisms that remove the drugs from circulation. Encouraging pre-clinical data demonstrates an attenuation of brain damage and increased structural and functional recovery. This review surveys the current progress in drug delivery for treating neonatal brain injury.

Keywords: Brain injury; Cerebral palsy; Hypoxic-ischemic encephalopathy; Infant; Nanoparticles; Targeted drug delivery.