PLGA-PEG-fucoxanthin nanoparticles protect against ischemic stroke in vivo

Fucoxanthin is the most abundant marine carotenoid derived from edible brown seaweeds and has been used as a functional ingredient for the treatment of obesity. However, poor brain bioavailability of fucoxanthin has limited its application in combating neurological diseases. In this study, we demonstrated that 40 % fucoxanthin was released from polylactic-co-glycolic acid-polyethylene glycol (PLGA-PEG) nanoparticles at one day after incubation. Fucoxanthin nanoparticles (20-40 mg/kg, i.v.) significantly prevented neurological and behavioral deficits in middle cerebral artery occlusion/reperfusion (MCAO)-treated rats via the reduction of M1 microglial activation, decrease of pro-inflammatory factor production, inactivation of the nuclear factor-kappa B (NF-kappa B) pathway, and elevation of the nuclear factor-E2-related factor 2 (Nrf2) pathway in ischemic penumbra. Moreover, fucoxanthin nanoparticles (5-15 mu g/mL) inhibited hypoxia-stimulated neurotoxicity in a mouse hippocampal neuron cell line (HT22 cells). These results suggest that fucoxanthin nanoparticles enhanced brain bioavailability and produced neuroprotection against ischemic stroke in vivo with much lower effective concentrations than fucoxanthin itself, providing further support for the development of fucoxanthin as a functional ingredient for the prevention of ischemic stroke with proper nanoparticle formulations.