Evolution of lipid nanoparticles as charioteers of Alzheimer's disease therapeutics

Alzheimer's disease (AD) is a global health crisis, one of the most complex neurodegenerative diseases that significantly affects populations worldwide without any age specificity. The development of AD is associated with the generation of intracellular amyloid β (Aβ) plaques and aggregation of tau proteins, leading to hyperphosphorylated microtubules, which cluster to form insoluble neurofibrillary tangles. Lipid nanoparticles (LNPs) have emerged as a promising tool in drug delivery, particularly for AD treatment. LNPs, as ideal nanocarriers, can encapsulate various therapeutic agents, such as peptides, drugs, and small molecules, all potential candidates for AD treatment. LNPs offer stability to encapsulated drugs, shielding them from degradation and premature release. Most importantly, LNPs can breach the blood-brain barrier (BBB), enabling targeted drug delivery to the central nervous system. In this review, we provide a comprehensive overview of various categories of drug-loaded LNPs that have been studied for AD treatment, including liposomes, niosomes, transferosomes, ethosomes, solid lipid nanoparticles, and nanostructured lipid carriers. We also emphasize the need for developing LNPs to facilitate the delivery of AD therapeutics across the BBB.