Revolutionizing Alzheimer's treatment: Harnessing human serum albumin for targeted drug delivery and therapy advancements

Alzheimer's disease (AD) is a neurodegenerative disorder initiated by amyloid-beta (Aβ) accumulation, leading to impaired cognitive function. Several delivery approaches have been improved for AD management. Among them, human serum albumin (HSA) is broadly employed for drug delivery and targeting the Aβ in AD owing to its biocompatibility, Aβ inhibitory effect, and nanoform, which showed blood-brain barrier (BBB) crossing ability via glycoprotein 60 (gp60) receptor and secreted protein acidic and rich in cysteine (SPARC) protein to transfer the drug molecules in the brain. Thus far, there is no previous review focusing on HSA and its drug delivery system in AD. Hence, the reviewed article aimed to critically compile the HSA therapeutic as well as drug delivery role in AD management. It also delivers information on how HSA-incorporated nanoparticles with surfaced embedded ligands such as TAT, GM1, and so on, not only improve BBB permeability but also increase neuron cell targetability in AD brain. Additionally, Aβ and tau pathology, including various metabolic markers likely BACE1 and BACE2, etc., are discussed. Besides, the molecular interaction of HSA with Aβ and its distinctive forms are critically reviewed that HSA can segregate Zn(II) and Cu(II) metal ions from Aβ owing to high affinity. Furthermore, the BBB drug delivery challenges in AD are addressed. Finally, the clinical formulation of HSA for the management of AD is critically discussed on how the HSA inhibits Aβ oligomer and fibril, while glycated HSA participates in amyloid plaque formation, i.e., β-structure sheet formation. This review report provides theoretical background on HSA-based AD drug delivery and makes suggestions for future prospect-related work.