Targeted Nanoparticles for Drug Delivery Across the Blood-Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review.

Alzheimer's disease (AD) presents important challenges for treatment. One significant factor that may reduce the effectiveness of therapy is the limited drug delivery to the brain due to the blood-brain barrier (BBB). Advancements in nanotechnology are offering innovative solutions to bypass this obstacle. This review highlights the role of targeted nanoparticles (NPs) as effective drug carriers across the BBB for both early and late stages of AD. The distinct pathophysiological traits of these stages-such as amyloid aggregation, abnormal accumulation of tau protein, neuroinflammation, and oxidative stress-are examined for their impact on therapy. The analysis includes lipid-based, polymeric, and inorganic NPs, exploring their unique properties for drug delivery. Strategies to target NPs to brain tissues affected by AD are discussed, emphasizing surface modifications to enhance BBB permeability. Uptake mechanisms like receptor-mediated and adsorptive-mediated transcytosis are detailed alongside safety, toxicity, and biocompatibility evaluations to assess clinical feasibility. Key findings indicate that targeted NPs significantly improve brain drug bioavailability and enable stage-specific therapeutic interventions, addressing challenges unique to early and late AD. Future research should focus on optimizing NP design for enhanced targeting specificity and minimizing long-term toxicity, ultimately paving the way for personalized nanomedicine approaches in AD treatment.