Surface engineered nano architectonics: An evolving paradigm for tackling Alzheimer's disease

As per the World Health Organization (WHO) estimation, Alzheimer's disease (AD) will affect 100 million population across the globe by 2050. AD is an incurable neurodegenerative disease that remains a mystery for neurologists owing to its complex pathophysiology. Currently, available therapeutic regimens will only cause symptomatic relief by improving the cognitive and behavioral functions of AD. However, the major pitfalls in managing AD include tight junctions in the endothelial cells of the blood-brain barrier (BBB), diminished neuronal bioavailability, enzymatic degradation and reduced stability of the therapeutic moiety. In an effort to surmount the drawbacks mentioned above, researchers shifted their focus toward nanocarriers (NCs). Nevertheless, non-specific targeting of NCs imparts toxicity to the peripheral organs, thereby reducing the bioavailability of therapeutic moiety at the target site. To unravel this unmet clinical need, scientists came up with the idea of a novel intriguing strategy of surface engineering by targeting ligands. Surface-decorated NCs provide targeted drug delivery, controlled drug release, enhanced penetration and bioavailability. In this state-of-the-art review, we have highlighted in detail various molecular signalling pathways involved in AD pathogenesis. The significance of surface functionalization and its application in AD management have been deliberated. We have elaborated on the regulatory bottlenecks and clinical hurdles faced during lab-to-industrial scale translation along with possible solutions.