Polyphenols in the Central Nervous System: Cellular Effects and Liposomal Delivery Approaches.

Neurodegenerative and neuroinflammatory diseases of the central nervous system are closely linked to aging and sustained oxidative and inflammatory stress. Polyphenols, plant-derived secondary metabolites, exhibit broad biological activities, including antioxidant and anti-inflammatory effects, the modulation of pathways such as PI3K/Akt, MAPK, Nrf2, and CREB, and the regulation of neurogenesis and microglial activation. This review focuses on the cell-specific actions of selected polyphenols in neurons, astrocytes, microglia, and oligodendrocytes within the context of Alzheimer's disease, Parkinson's disease, and multiple sclerosis. A major limitation to the therapeutic use of polyphenols is their poor bioavailability, due to instability, low solubility, and limited blood-brain barrier penetration. Liposomal nanocarriers are explored as promising delivery systems to overcome these barriers. Both conventional and functionalized liposomes (e.g., PEGylated, receptor-targeted) are discussed, alongside in vitro and in vivo studies demonstrating enhanced efficacy compared to free compounds. Intranasal delivery is also presented as a viable alternative to oral administration. Overall, polyphenols offer great potential as neuroprotective agents, and liposome-based delivery platforms have the potential to significantly enhance their clinical potential, provided that key formulation and targeting issues are addressed.