ALZHEIMER’S DISEASE: DELIVERY OF DRUGs THROUGH INTRANASAL ROUTE

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by severe cognitive impairments. A major histopathological hallmark of AD is the presence of amyloid deposits in the parenchyma of the amygdala, hippocampus, and neocortex. β-amyloid is a small piece of a larger protein called "amyloid precursor protein" (APP). The main component of amyloid is the β-Amyloid protein (Aβ), a 39.43 amino acid peptide composed of a portion of the transmembrane domain and the extracellular domain of the APP. Aβ deposition leads to synaptic degeneration and interacts with different types of central nervous system receptors; hence, it disrupts neuronal homeostasis. Moreover, Aβ deposition along the cerebral vessels alters their tonicity and triggers some of the cerebrovascular deficits. Furthermore, its accumulation disrupts intracellular Ca2+ homeostasis which ultimately reduces neuronal Ca2+ buffering capacity and increases excitotoxicity outcomes. The emerging approach is to bypass the BBB by intranasal delivery, which provides a practical, noninvasive, rapid and simple method to deliver the therapeutic agents to the CNS. This method works the unique connection between the nose and the brain that has evolved to sense odors and other chemical stimuli. On the basis of clinical trials (Phase I and II) it is reported that the intranasal route is feasible for the transport of the drug to the CNS. Intranasal delivery does not require any modification of the therapeutic agents and does not require that drugs be coupled with any carrier like in case of drug delivery across the BBB. A wide variety of therapeutic agents, including both small molecules and macromolecules can be successfully delivered, including to the CNS, using the intranasal method.

Potential Anti-Acetylcholinesterase Activity of Cassia timorensis DC.

“…It is characterized by consistent loss of neurons in the cognitive system, the appearance of amyloid plaques, intercellular hyper-phosphorylated neurofibrillary tangles (NFTs), and an inadequate level of acetylcholine (ACh), a neurotransmitter in the brain [ 11 ]. The acetylcholinesterase enzyme (AChE) has an important role in the treatment of AD, where impediment of its activity (hydrolyzing the acetylcholine (ACh) neurotransmitter into choline and acetate) will help to maintain the longevity of the neurotransmitter in the cerebral cortex [ 12 , 13 ]. ACh transports signals within neurons and it significantly contributes to memory and learning.…”