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

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.

Recent developments in solid lipid nanoparticle and surface-modified solid lipid nanoparticle delivery systems for oral delivery of phyto-bioactive compounds in various chronic diseases

“…[92][93][94][95][96] Initially, SLN-or MSLN-loaded bioactive compounds were given intranasally or intravenously, and these showed extensive bioavailability in the brain, thereby preventing inflammation and further progression of AD. [97][98][99][100][101] Quercetin-loaded SLN with a particle size of about 200 nm was studied for its efficacy in the AD model, and it showed excellent delivery of quercetin to the brain with a higher antioxidative effect in brain cells.…”

“…In another study, resveratrol-loaded SLN with functionalized antibody showed excellent cellular uptake compared to normal SLN. 93 Many other phyto-bioactive compounds loaded onto SLNs or MSLNs are still in the development pipeline with a size suitable for effective transport through the blood-brain barrier, and these can result in higher protection of brain cells to overcome age-related degenerative diseases. 195 …”

Solid lipid nanoparticles: a promising technology for delivery of poorly water-soluble drugs

“…SLN-antibody conjugation was used for the delivery of grape extract with resveratrol to the brain to treat Alzhimer disease by inhibiting amyloid-β peptide aggregation. The cellular uptake was found to be higher in SLN-antibody conjugation than the normal SLN 67 . The surface modification of SLN with apolipoprotein E-derived peptide (SLN-mApoE) was efficiently crossed the blood-brain barrier when tested using in-vitro model by Dal et al The more confinement in the brain was found after pulmonary administration of SLN-mApoE, when compared to intravenous and intraperitoneal administration 68 .…”

Lipid nanocarriers loaded with natural compounds: Potential new therapies for age related neurodegenerative diseases?

“…Therefore, these multifunctional formulations could be used for theranostic (therapy by curcumin neuroprotective effect and diagnostic by curcumin labelling of Aβ deposits) purposes (Mourtas et al, 2014). The same strategy of targeting TfR with OX-26 antibody was used in SLN loaded with resveratrol from grape skin and grape seed extracts (Loureiro et al, 2017). OX-26 functionalization increased uptake of resveratrol loaded SLN by BBB cell model and transcytosis across the BBB cell model when compared with SLN functionalized with another antibody (LB 509) or with non-functionalized SLN (Loureiro et al, 2017).…”