Advances in Strategies to Transport Nanoparticles Across the Blood-Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by progressive dementia, constituting one of the leading causes of global mortality. Although the current treatments help attenuate the symptoms associated with AD, they are unable to stop the long-term progression of the disease, and consequently, no cure exists. One of the main reasons for the lack of cure and, therefore, one of the biggest challenges in its treatment, is the blood-brain barrier (BBB). This protective barrier limits the entry of foreign substances, including drugs, into the central nervous system. Different types of engineered nanoparticles (NPs) have been demonstrated to be able to penetrate this barrier and serve as efficient drug delivery systems (DDS) into the brain, making them a promising solution for future therapeutic development. Therefore, the purpose of this paper is to provide valuable insights into challenges faced by DDS in treating AD, highlight the nanotechnology-based approach, and discuss the advances in strategies being employed to enhance the crossing of NPs through the BBB. Furthermore, some up-to-date NP systems are presented, along with the latest therapeutic agents targeting AD, and finally, it underscores innovative approaches under investigation. Ultimately, the barriers hindering the clinical translation of NP-based strategies into human patients are discussed.