Curcumin nanoformulations for modulating neuroinflammation and oxidative stress in Alzheimer's disease: blood-brain barrier transport, formulation strategies and therapeutic applications.

Alzheimer's disease (AD) remains a major therapeutic challenge owing to its complex and multifactorial pathogenesis, as well as the limited clinical efficacy of conventional therapeutics caused by poor pharmacokinetic properties, rapid systemic clearance, and restricted transport across the blood-brain barrier (BBB). Curcumin, a naturally derived polyphenolic compound, has gained considerable attention as a potential therapeutic agent for AD due to its broad neuroprotective and disease-modifying properties. Curcumin has been reported to inhibit amyloid-β (Aβ) aggregation and fibril formation, destabilize preformed amyloid plaques, suppress tau protein aggregation, reduce oxidative stress-induced neuronal damage, preserve mitochondrial integrity, modulate metal ion-induced neurotoxicity, and protect neuronal cells against apoptosis. Despite these promising therapeutic effects, the clinical translation of curcumin remains significantly limited by poor aqueous solubility, low chemical stability, rapid metabolism, limited systemic bioavailability, and insufficient BBB permeability. This review critically summarizes recent advances in curcumin-based nanocarrier systems for brain-targeted delivery in AD, with particular emphasis on pharmaceutical formulation strategies, physicochemical characterization, encapsulation efficiency, controlled drug release, colloidal stability, and preclinical therapeutic performance. Particular attention is given to the ability of curcumin nanoformulations to modulate neuroinflammatory pathways, including microglial activation, pro-inflammatory cytokine production, oxidative stress, and NLRP3 inflammasome signaling, which are central contributors to AD progression. This review focuses on polymeric nanoparticles, liposomes, nanoemulsions, and biomimetic nanoplatforms engineered to enhance BBB transport and improve brain biodistribution. Collectively, nanocarrier-mediated curcumin delivery represents a promising pharmaceutical strategy to improve brain-specific bioavailability and enable effective multitarget therapeutic intervention in AD.