Brain‐targeted N‐Acetyl Cysteine‐loaded nanoparticle for AD treatment

Abstract Background The microglia activation‐induced neuroinflammation is one potential cause of Alzheimer’s disease (AD). N‐Acetyl cysteine (NAC), which has anti‐oxidant and anti‐inflammatory effects, has been extensively explored for the treatment of of AD. However, its therapeutic efficacy for AD is limited due to the existence of the blood‐brain barrier (BBB). Method To facilitate NAC cross the BBB, a brain‐targeted NAC‐loaded nanoparticle (BTN‐NAC) has been developed. The brain‐targeting efficacy and therapeutic efficacy of BTN‐NAC were evaluated in a 5xFAD transgenic mouse model through nest construction assay and Morris water maze test. Result In vivo study revealed that BTN‐NAC could effectively cross the BBB of AD mice. Nest construction assay found that BTN‐NAC treated AD mice exhibited better nesting score than free NAC and control treated mice. In addition, BTN‐NAC treatment significantly improved the learning and cognitive skills of AD mice. Immunohistochemical staining confirmed that BTN‐NAC effectively inhibited the activation of microglia in the brain and attenuated the deposition of Aβ plaques in the hippocampus. Conclusion BTN‐NAC can effectively cross the BBB, prevent the activation of microglia, and attenuate Aβ burden in the brain of AD mice. Consequently, BTN‐NAC slows down the progress of AD. Therefore, BTN‐NAC could be safe and effective tool for the treatment of AD.