Nanoparticle-conjugated nutraceuticals exert prospectively palliative of amyloid aggregation

Abstract

Alzheimer’s disease (AD), an age-related neurodegenerative disease, the most common causes of dementia is a multifactorial pathology categorized by a complex etiology. Numerous nutraceuticals have been clinically evaluated, but some of the trials failed. However, natural compounds have some limitations due to their poor bioavailability, ineffective capability to cross the blood–brain barrier, or less therapeutic effects on AD. To overcome these disadvantages, nanoparticle-conjugated natural products could promote the bioavailability and enhance the therapeutic efficacy of AD when compared with a naked drug. This application generates and implements new prospect for drug discovery in neurodegenerative diseases. In this article, we confer AD pathology, review natural products in clinical trials, and ascertain the importance of nanomedicine coupled with natural compounds for AD.

Functionalization strategies of polymeric nanoparticles for drug delivery in Alzheimer’s disease: Current trends and future perspectives

“…Resveratrol showed antioxidant activity and anti-Aβ formation features both in vivo , in Tg2576 mice, and in vitro through different molecular mechanisms, including inhibition of β-amyloid-induced neuronal apoptosis via regulation of the silent information regulator 1 (SIRT1)-Rho-associated kinase 1 (ROCK1) signaling pathway in PC12 cells and by promoting non-amyloidogenic processing of APP, and thus mitigating Aβ neuropathology in AD ( Wang et al, 2006 ; Ladiwala et al, 2010 ; Feng et al, 2013 ). However, recent AD clinical trials with natural compounds, including curcumin and resveratrol as well, failed in different phases to successfully treat AD ( Kanubaddi et al, 2018 ). This has been partially due to the low aqueous solubility, poor bioavailability, and ineffectiveness against the disease mainly because of the low penetration of resveratrol and other natural molecules across the BBB; whereby the need of alternative NP-based formulations for improving pharmacokinetic properties, bioavailability, neural targetability and the great clinical potential of these nutraceuticals ( Summerlin et al, 2015 ; Kanubaddi et al, 2018 ).…”

Inorganic Nanomaterials versus Polymer-Based Nanoparticles for Overcoming Neurodegeneration

“…It was demonstrated that resveratrol is efficient in the attenuation of neuronal injuries and the modulation of neuronal signaling and glial pathways, as well as in the autophagy process [ 7 ]. Furthermore, resveratrol nanocarriers obtained by encapsulating or conjugating it in SLNs or nanocapsules, have shown improved solubility and a slower metabolism associated with their capability to efficiently target and inhibit the formation/aggregation of Aβ peptides [ 59 ]. Kanubaddi and colleagues reported improvements in the stability and solubility (dependent on the hydrophobic nature) of curcumin, a turmeric derivative belonging to the ginger family, which can bind to and dissolve Aβ aggregates when conjugated with AuNPs, nanogels, polymeric NPs, and nanoliposomes [ 59 ].…”

<p>Innovative Therapies and Nanomedicine Applications for the Treatment of Alzheimer’s Disease: A State-of-the-Art (2017–2020)</p>

“…Today (April, 14 th 2020) in PUBMED database, a search through the keywords "nutraceutical" and "Alzheimer" retrieves more than 200 papers in a limited selection to the last five years, but only 1 (a review) if the keyword "nanomedicine" or "nanoparticle" was added. 85 This indicates that a comprehensive revision of the literature in this field is lacking and that dedicated reviews may be needed. Here, only the more recent advances in this field are indicated ( Table 2).…”

“…Data showed how resveratrol could reach the brain and inhibit the formation and aggregation of Aβ peptides. 8,85 Another very interesting flavonoid is quercetin. Its applications are best studied in targeting cancer.…”

“…Kanubaddi and colleagues reported improvements in its solubility, stability, and ability to bind and dissolve Aβ aggregates when conjugated with AuNPs, nanogels, polymeric NPs, and nanoliposomes. 85 More recently, natural micellar-forming polymers, such as casein, have attracted interest in the development of micelle delivery system thanks to their safety, biodegradability, and ability to not affect the immune system. Many casein-based pharmaceutical products are in clinical evaluation.…”