Navigating neurodegeneration: challenges, pathophysiology, biomarkers, and the promise of nanocrystals-based...

Approximately 90% of drugs struggle with low solubility and non-selectivity in target-specific drug delivery. This creates a significant challenge due to the limited permeability of the blood-brain barrier (BBB) and blood-cerebrospinal fluid (CSF) barrier. Poor solubility, low drug concentration at the target site, and rapid clearance via efflux transporters further restrict effective drug delivery in neurodegenerative disorders (NDDs). Nanocrystal (NC) technology offers a promising approach by producing sub-micron, carrier-free NCs with high drug payload, stabilised with stabilisers to enhance colloidal stability and shelf life. The increased surface area boosts the solubility, bioavailability, and brain permeability of hydrophobic drugs, making NCs an emerging technology for both therapeutic and diagnostic applications in neurodegenerative diseases. NCs are synthesised via top-down, bottom-up, and combinational methods, with NANOEDGE^® and SmartCrystals^® being some of the patented technologies. Despite the high potential of NCs in improving drug delivery to the brain, many challenges remain, including thermal instability, scalability, and long-term safety.