Uptake of dendrimer-drug by different cell types in the hippocampus after hypoxic-ischemic insult in neonatal mice: Effects of injury, microglial activation and hypothermia

Hydroxyl polyamidoamine dendrimers are being explored for targeted delivery of therapy for hypoxic-ischemic encephalopathy. We examined cellular uptake of N-acetyl-L-cysteine conjugated to Cy5-labeled dendrimer in a neonatal mouse model of hypoxic-ischemic encephalopathy, with or without therapeutic hypothermia. Dendrimer conjugation delivered therapy most effectively to activated microglia but also targeted astrocytes and injured neurons. Uptake correlated with brain injury and with activated morphology in microglia. Uptake was not impaired by hypothermia, except in CD68+ microglia; thus, dendrimer delivery can be combined with therapeutic hypothermia.321