Nutraceuticals and their Derived Nano-formulations for the Prevention and Treatment of Alzheimer's disease.

Alzheimer's disease is one of the common chronic neurological disorders and associated with cognitive dysfunction, depression and progressive dementia. Presence of β-amyloid or senile plaques, hyper-phosphorylated tau proteins, neurofibrillary tangle, oxidative-nitrative stress, mitochondrial dysfunction, endoplasmic reticulum stress, neuroinflammation and derailed neurotransmitter status are the hallmark of AD. Currently, donepezil, memantine, rivastigmine and galantamine are approved by the FDA for symptomatic management. It is well-known that these approved drugs only exert symptomatic relief and possess poor patient-compliance. Additionally, various published evidence shows the neuroprotective potential of various nutraceuticals via their antioxidant, anti-inflammatory and anti-apoptotic effects in the preclinical and clinical studies. These nutraceuticals possess a significant neuroprotective potential and hence, can be a future pharmacotherapeutic for the management and treatment of AD. However, nutraceutical suffers from certain major limitations such as poor solubility, low bioavailability, low stability, fast hepatic-metabolism and larger particle size. These pharmacokinetic attributes restrict their entry into the brain via the blood-brain barrier. Therefore, to over such issues, various nanoformulation of nutraceuticals was developed, that allows their effective delivery into brain owning to reduced particle size, increased lipophilicity increased bioavailability and avoidance of fast hepatic metabolism. Thus, in this review, we have discussed the etiology of AD, focused on the pharmacotherapeutics of nutraceuticals with preclinical and clinical evidence, discussed pharmaceutical limitation and regulatory aspects of nutraceuticals to ensure safety and efficacy. We further explored the latitude of various nanoformulation of nutraceuticals as a novel approach to overcome the existing pharmaceutical limitation and for effective delivery into the brain.