Therapeutics: Advancements in the Application of Nanomedicine in Alzheimer’s Disease

Alzheimer’s is the most common cause of dementia, a general term for memory loss and other cognitive abilities serious enough to interfere with daily life. The greatest known risk factor is increasing age, and most people with Alzheimer’s are 65 and older. Alzheimer’s is a progressive disease, where dementia symptoms
gradually worsen over several years. In its early stages, memory loss is mild, but with late-stage Alzheimer’s, individuals lose the ability to carry on a conversation and respond to their environment. Two abnormal structures called plaques and tangles are prime suspects in damaging and killing nerve cells.

1. Plaques are deposits of a protein fragment call beta-amyloid that build up in the spaces between nerve cells.
2. Tangles are twisted fibres of another protein called tau that build up inside cells.

A buildup of toxic amyloid-beta peptide and amyloid plaques can lead to the death of nerve cells and the symptoms of Alzheimer’s disease. As amyloid plaques collect in the brain, proteins called tau proteins don’t work as they should. Instead, they stick together to form tau tangles. These tangles are linked to how Alzheimer’s disease affects the brain.

Another feature is the loss of connections between nerve cells (neurons) in the brain. Damage initially takes place in parts of the brain involved in memory, including the entorhinal cortex and hippocampus. It later affects areas in the cerebral cortex, such as those responsible for language, reasoning, and social behaviour. Eventually, many other areas of the brain are damaged.

According to Lamptey, R.N.L.; Chaulagain, B.; Trivedi, R. et.al; Int. J. Mol. Sci. 2022, Mental and CNS illnesses have a significant prevalence worldwide, including neuroinflammation, brain tumours, and NDs. Neuronal loss is the main characteristic of NDs. AD and PD are the most common NDs. Although several
medications are now approved for managing NDs, most treat only the related symptoms. Because of the presence of the BBB, developing therapeutic agents for various CNS-related disorders is highly challenging as described by Kimura, S.; Harashima, H. in Pharmaceutics 2020.

Clinical trials conducted by Ren, J.; Jiang, F.; Wang, M.; et.al in Biomater. Sci. 2020 shows that the BBB (Blood Brain Barrier) serves as the primary barrier to drug delivery in AD treatment. The physical and biochemical barriers of the BBB limit the effects of all hydrophilic drugs; efflux pumps inside the BBB frequently transfer lipophilic drugs back into the blood. Studies by Ding, S.; Khan, A.I.; Cai, X.; et.al in Mater. Today 2020 and Hersh, A.M.; Alomari, S.; Tyler, B.M. in Int. J. Mol. Sci. 2022 showed that as a result, it is critical to understand the structure and activity of the BBB to suggest alternative methods for delivering AD medications via nano-DDS. Utilizing the endothelial cell-binding affinity of lipid-soluble NPs can increase the rate at which a drug is transported via endocytosis or lipophilic transcellular routes. Moreover, the adsorptive properties of NPs can be useful because they can adhere to blood capillaries in the BBB, boosting the likelihood that the target medicine will cross this barrier.

Saucier-Sawyer, J.K.; Deng, Y.; Seo, Y.E.; et.al in J. Drug Target. 2015, found that altering NPs with specific receptors, carrier proteins, and receptor-mediated transcytosis can enhance medication uptake through the BBB. Despite the ability of NPs to pierce the BBB, only approximately 5% of medications reach the brain,
leaving the remaining 95% at an ineffective location. But when this was cross studied by Ling, T.S.; Chandrasegaran, S.; Xuan, L.Z.; et.al in Biomed. Res. Int. 2021 this phenomenon was found to cause systemic side effects because the conventional route of drug administration is ineffective for accurately delivering the agent to the brain. The transport of therapeutic substances to the CNS via the olfactory and trigeminal nerves of the nasal cavity is facilitated by intranasal administration. Furthermore, intranasal administration is riskfree and non-invasive. This medicine can prevent hepatic first-pass metabolism and drug degradation, increasing drug bioavailability.

Nanotechnology is a cutting-edge method that may open the door to new ways to overcome blood–CNS barriers, particularly the BBB. The therapeutic effects of drug delivery systems depend on their capacity to bypass the immune system, pass through the BBB, and locate themselves in the target tissues. NPs are widely used in the diagnosis and treatment of AD as put forward by the findings of Bashir, W.; Shahzadi, S. in J. Appl. Biotechnol. Bioeng. 2022 however, for successful results, several aspects must be considered, including the target-specific distribution and metabolism of NPs and the interactions between target molecules (Aβ/Tau/NFT) and NPs.

As described by Harish, V.; Tewari, D.; Gaur, M.; et.al in Nanomaterials 2022, Nanomaterials have good in vitro inhibitory efficiency; however, the in vivo inhibition efficiency needs to be increased. Several metallic NPs were found to provide a good platform for efficient inhibition of the aggregation of Aβ either directly or after conjugation with a drug molecule by the research conducted and published by Chakraborty, A.; Mohapatra, S.S.; Barik, S.; et.al in Biosci. Rep. 2023