Background: The role of Fe+2, Cu+2 and Zn+2 in facilitating aggregation of Amyloid β (Aβ)
and consequently, the progression of Alzheimer's disease (AD) is well established.
Objective: Development of non-toxic metal chelators is an emerging era in the treatment of AD, in
which complete success has not been fully achieved. The purpose of this study was to determine plant
extracts with high metal chelator and to encapsulate them in nano-micellar systems with the ability to
pass through the Blood Brain Barrier (BBB).
Methods: Extracts of 36 different Anatolian plants were prepared, total phenolic and flavonoid contents
were determined, and the extracts with high content were examined for their Fe+2, Cu+2 and Zn+2
chelating activities. Apolipoprotein E4 (Apo E) decorated nano-formulations of active extracts were
prepared using Poly (Lactide-co-Glycolide) (PLGA) (final product ApoEPLGA) to provide BBB penetrating
Results: Verbascum flavidum aqueous extract was found as the most active sample, incubation of
which, with Aβ before and after metal-induced aggregation, resulted in successful inhibition of aggregate
formation, while re-solubilization of pre-formed aggregates was not effectively achieved. The
same results were obtained using ApoEPLGA.
Conclusion: An optimized metal chelator nano-formulation with BBB penetrating ability was prepared
and presented for further in-vivo studies.