Targeted Delivery of Omega-3 Fatty Acids using Cyclodextrin-Based Nanosponges: Therapeutic Potential in Neurodegenerative Diseases

The increasing incidence of neurodegenerative diseases including multiple sclerosis, Parkinson's disease, and Alzheimer's disease worldwide has brought attention to the need for efficient therapeutic treatments. Among other potential nutraceuticals, omega-3 fatty acids have become potent neuroprotective agents because of their antiinflammatory, antioxidant, and membrane-stabilizing properties. However, oxidative instability, limited bioavailability, poor water solubility, and nonspecific distribution in the central nervous system (CNS) hinder their therapeutic use. To overcome these limitations, novel nanocarrier systems are being explored, among which cyclodextrin-based nanosponges (CD-NS) have gained significant attention. This review explores the innovative application of CD-NS as an advanced platform for the targeted delivery of Omega-3 fatty acids to the brain. Cyclodextrins, with their unique hydrophilic outer surface and hydrophobic core, facilitate encapsulation of lipophilic molecules like Omega-3s, while nanosponge cross-linking enhances stability, controlled release, and brain-specific targeting. We critically discuss the synthesis strategies, physicochemical characteristics, and surface modifications of CD-NS that improve blood-brain barrier permeability and prolong systemic circulation. Furthermore, this paper elaborates on mechanistic insights into how Omega-3s modulate neuroinflammatory pathways, protect neuronal integrity, and support neurogenesis when delivered via nanosponges. Through a comparative analysis of conventional versus nanosponge-mediated delivery systems, the review underscores the superiority of CD-NS in overcoming pharmacokinetic barriers. Preclinical evidence and recent in vivo studies are highlighted to validate the neurotherapeutic efficacy of this nanotechnology-based delivery approach. By bridging the gap between nutraceutical science and nanomedicine, this review aims to inspire students, researchers, and pharmaceutical innovators to further investigate cyclodextrin nanosponges as a promising frontier in targeted therapy for neurodegenerative diseases. The integration of bioactive lipids and smart nanocarriers could redefine the landscape of CNS drug delivery