Nanocarriers in Alzheimer's Therapy: A Comprehensive Review on Nanoparticulate Drug Delivery Systems

Neurodegenerative disorders, particularly Alzheimer's Disease (AD), pose a major global health challenge, characterized by progressive neuronal degeneration and cognitive decline. The blood-brain barrier (BBB) significantly limits the efficacy of conventional therapeutics, preventing adequate drug delivery to the central nervous system. Nanoparticulate Drug Delivery Systems (NPDDS) have emerged as a promising approach to overcome these limitations and enhance the therapeutic potential of AD interventions.

This review comprehensively examines recent advancements in NPDDS for AD therapy. Various nanoparticle classes, including polymeric nanoparticles, solid lipid nanoparticles, gold nanoparticles, liposomes, microemulsions/nanoemulsions, dendrimers, and hydrogels, are evaluated with respect to their physicochemical characteristics, drug-loading capacities, BBBpenetrating strategies, and potential for targeted cerebral delivery. Relevant preclinical and clinical studies were analyzed to summarize the pharmacokinetic and pharmacodynamic benefits of these systems.

The reviewed NPDDS demonstrate enhanced drug solubility, stability, and controlled release profiles. Multiple strategies, such as surface functionalization, intranasal administration, and receptor-mediated transcytosis, facilitate BBB penetration and site-specific drug delivery. Nanocarriers improve drug accumulation at pathological sites, potentially enhancing therapeutic efficacy while reducing systemic side effects. Each nanoparticle class offers distinct advantages: polymeric and lipid-based systems provide controlled release and biocompatibility, while metallic and dendrimeric platforms offer theranostic capabilities and high drug-loading potential.

Despite their promise, challenges remain in translating NPDDS to clinical applications. Efficient and reproducible BBB crossing, potential cytotoxicity, long-term biocompatibility, and scalable manufacturing processes require further optimization. Multifunctional and hybrid nanocarriers, stimuli-responsive systems, and biomimetic designs are emerging to address these limitations. Continuous advancements in nanotechnology offer tunable physicochemical properties to tackle the complex pathogenesis of AD, enabling more precise, effective, and patient- compliant therapies.

NPDDS represent a transformative frontier in Alzheimer's disease management, offering targeted, efficient, and adaptable drug delivery solutions. Strategic development and rigorous evaluation of these systems may improve CNS bioavailability of therapeutic agents, enhance clinical outcomes, and potentially shift the paradigm in the treatment of neurodegenerative disorders. Future research should focus on overcoming translational challenges to realize the full potential of nanocarrier-based AD therapy.