Indirubin-3′-monoxime-loaded PLGA-PEG nanoparticles for potential Alzheimer's disease treatment

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder, which is pathologically characterized by the deposits of β-amyloid (Aβ), and plays an important role in neuronal death. Indirubin-3′-monoxime (I3M) showed neuroprotective effects against Aβ-induced neuronal apoptosis. However, the use of I3M in AD treatment is limited due to its low bioavailability. Herein, PLGA-PEG nanoparticles were synthesized for I3M loading. I3M could release sustainedly sustain release from the I3M-loaded PLGA-PEG nanoparticles (PLGA-PEG-I3M NPs) without obvious burst release. What's more, the PLGA-PEG-I3M NPs could significantly promote the uptake of I3M by PC12 ​cells through nanoparticle-mediated transport, and improve the efficacy of I3M on the inhibition of Aβ fibrillization and oligomerization as well as the neuroprotective activity of I3M on Aβ oligomers-induced neuronal death. Thus, the PLGA-PEG-I3M NPs may be a promising platform for AD therapy.