TY - JOUR
T1 - Novel Curcumin loaded nanoparticles engineered for Blood-Brain Barrier crossing and able to disrupt Abeta aggregates
AU - Barbara, Ruozi
AU - Belletti, Daniela
AU - Pederzoli, Francesca
AU - Masoni, Martina
AU - Keller, Johannes
AU - Ballestrazzi, Antonio
AU - Vandelli, Maria Angela
AU - Tosi, Giovanni
AU - Grabrucker, Andreas M.
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/6/30
Y1 - 2017/6/30
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Amyloid
KW - BBB targeting nanoparticles
KW - Curcumin
KW - Nanotechnology
KW - Synapse
UR - http://www.scopus.com/inward/record.url?scp=85019185474&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2017.05.015
DO - 10.1016/j.ijpharm.2017.05.015
M3 - Article
C2 - 28495580
AN - SCOPUS:85019185474
SN - 0378-5173
VL - 526
SP - 413
EP - 424
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -