The formation of extracellular aggregates built up by deposits of β-amyloid (Aβ) is a hallmark
of Alzheimer’s disease (AD). Curcumin has been reported to display anti-amyloidogenic
activity, not only by inhibiting the formation of new Aβ aggregates, but also by
disaggregating existing ones. However, the uptake of Curcumin into the brain is severely
restricted by its low ability to cross the blood-brain barrier (BBB). Therefore, novel strategies
for a targeted delivery of Curcumin into the brain are highly desired. Here, we encapsulated
Curcumin as active ingredient in PLGA (polylactide-co-glycolic-acid) nanoparticles (NPs),
modified with g7 ligand for BBB crossing. We performed in depth analyses of possible
toxicity of these NPs, uptake, and, foremost, their ability to influence Aβ pathology in vitro
using primary hippocampal cell cultures. Our results show no apparent toxicity of the
formulated NPs, but a significant decrease of Aβ aggregates in response to Curcumin loaded NPs. We thus conclude that brain delivery of Curcumin using BBB crossing NPs is a
promising future approach in the treatment of AD.