Resveratrol and Grape Extract-loaded Solid Lipid Nanoparticles for the Treatment of Alzheimer's Disease.

Joana Loureiro,Stephanie Andrade,Joana Queiroz,Joana Queiroz,Ana Duarte,Maria Pereira,Cláudia Nunes,Laurence Fenart,Ana Neves,Ana Neves,Fabien Gosselet,Emmanuel Sevin,Manuel Coelho

doi:10.3390/molecules22020277

Abstract

The aggregation of amyloid-β peptide (Aβ) has been linked to the formation of neuritic plaques, which are pathological hallmarks of Alzheimer’s disease (AD). Various natural compounds have been suggested as therapeutics for AD. Among these compounds, resveratrol has aroused great interest due to its neuroprotective characteristics. Here, we provide evidence that grape skin and grape seed extracts increase the inhibition effect on Aβ aggregation. However, after intravenous injection, resveratrol is rapidly metabolized into both glucuronic acid and sulfate conjugations of the phenolic groups in the liver and intestinal epithelial cells (within less than 2 h), which are then eliminated. In the present study, we show that solid lipid nanoparticles (SLNs) functionalized with an antibody, the anti-transferrin receptor monoclonal antibody (OX26 mAb), can work as a possible carrier to transport the extract to target the brain. Experiments on human brain-like endothelial cells show that the cellular uptake of the OX26 SLNs is substantially more efficient than that of normal SLNs and SLNs functionalized with an unspecific antibody. As a consequence, the transcytosis ability of these different SLNs is higher when functionalized with OX-26.

Highlights

Alzheimer’s disease (AD) is classified as the most common form of dementia, accounting more than 80% of dementia cases worldwide [1]
In the presence of β-sheet fibrils, Thioflavin T (ThT) can at a molar ratio of 5:8 and 5:16 (Aβ(1–42):resveratrol or extracts) was evaluated by the ThT binding assay enter into cavities produced by the quaternary structure of the protein binding with the protein
At the concentration of 80 μM, these values increased for 91%, 97% and 98%, respectively

Summary

Introduction

Alzheimer’s disease (AD) is classified as the most common form of dementia, accounting more than 80% of dementia cases worldwide [1]. Evidences support a direct association between the degree of dementia of patients that have AD and the concentration of soluble aggregates of Aβ peptide [2,3,4]. The aggregation process of Aβ leads to the formation of insoluble fibrils that have a beta-sheet structure, which accumulate as senile plaque deposits that characterize AD [5,6]. The more abundant sequences of the peptide have 40 (~90%), Aβ(1–40) , and 42 (~10%), Aβ(1–42) , amino acids [7]. Aβ(1–42) is more toxic and it is the major component of the neuritic plaques found in AD [8,9]. One possible approach to Molecules 2017, 22, 277; doi:10.3390/molecules22020277 www.mdpi.com/journal/molecules

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