Organometallic Therapeutics and Drug Delivery Strategies for Alzheimer's Disease: Bridging Metal Chemistry and Neurodegeneration

Abstract

Alzheimer's disease (AD) remains one of the most challenging neurodegenerative disorders to treat due to its multifactorial pathology and limited efficacy of current therapies. Although recent advances have focused on amyloid-targeting strategies, effective disease modification is hindered by poor brain penetration, unfavorable pharmacokinetics, and inability to address multiple pathological pathways simultaneously. Organometallic-based drug delivery systems have emerged as promising multifunctional platforms that combine the unique properties of metal-containing compounds with advanced nanocarrier technologies. This review highlights recent developments in organometallic therapeutics and delivery strategies for AD, focusing on pharmaceutical design, blood-brain barrier transport, controlled drug release, and neurotherapeutic potential. Various delivery platforms, including nanoparticles, liposomes, dendrimers, polymer conjugates, and metal-organic frameworks, are discussed in relation to their ability to enhance drug stability, biodistribution, targeting efficiency, and therapeutic efficacy. The therapeutic relevance of these systems is further examined through their capacity to modulate amyloid-β aggregation, oxidative stress, metal dyshomeostasis, tau pathology, and neuroinflammation. Preclinical evidence suggests that organometallic-based platforms offer advantages over conventional approaches by integrating targeted delivery with intrinsic therapeutic activity. Despite challenges related to safety, scalability, and regulatory translation, continued advances in material design and translational research may facilitate development of clinically viable disease-modifying therapies for AD.