Nano-formulated curcumin uptake and biodistribution in the fetal growth restricted newborn piglet brain.

Fetal growth restriction (FGR) affects 5% to 10% of all pregnancies in developed countries and is the second most leading cause of perinatal mortality and morbidity. Life-long consequences of FGR range from learning and behavioral issues to cerebral palsy. To support the newborn brain following FGR, timely and accessible neuroprotection strategies are needed. Curcumin-loaded polymeric nanoparticles, which have been widely explored for the treatment of cancer, neurological disorders, and bacterial infections, have the potential to prevent and mitigate pathogenic inflammatory processes in the FGR brain. Curcumin is a hydrophobic molecule with poor aqueous solubility and therefore has been incorporated into nanoparticles to improve solubility and delivery. However, curcumin loading in many nanoparticles can be limited to 10% by weight or lower. Here, we first optimize the formulation process of curcumin-loaded polymeric nanoparticles to find a tunable, reproducible, and stable formulation with high curcumin loading and encapsulation efficiency. We establish a curcumin formulation with 39% curcumin loading and > 95% curcumin encapsulation efficiency. Using this formulation, we assessed the biodistribution of polymeric nanoparticles in FGR piglets and normally grown (NG) piglets following different administration routes and evaluated brain cellular uptake. We show a significant amount of nanoparticle accumulation in the brain parenchyma of neonatal piglets as early as 4 h after intranasal administration. Nanoparticles colocalized in microglia, a therapeutic target of interest in FGR brain injury. This study demonstrates the potential of curcumin-loaded nanoparticles to treat neuroinflammation associated with FGR in the newborn.