Abstract
:
Alzheimer’s disease (AD) is one of the common chronic neurological disorders and associated
with cognitive dysfunction, depression and progressive dementia. The 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 hallmarks 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 showed 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, nutraceuticals suffer
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 overcome such issues, various nanoformulations of
nutraceuticals have been developed, that allow their effective delivery into the brain owing 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, focusing on the pharmacotherapeutics
of nutraceuticals with preclinical and clinical evidence, discussed pharmaceutical
limitations and regulatory aspects of nutraceuticals to ensure safety and efficacy. We have further
explored various nanoformulations of nutraceuticals as a novel approach to overcome the existing
pharmaceutical limitations and for effective delivery into the brain.