Recent Uses of Lipid Nanoparticles, Cell-Penetrating and Bioactive Peptides for the Development of Brain-Targeted Nanomedicines against Neurodegenerative Disorders.

The lack of effective treatments for neurodegenerative diseases (NDs) is an important current concern. Lipid nanoparticles can deliver innovative combinations of active molecules to target the various mechanisms of neurodegeneration. A significant challenge in delivering drugs to the brain for ND treatment is associated with the blood-brain barrier, which limits the effectiveness of conventional drug administration. Current strategies utilizing lipid nanoparticles and cell-penetrating peptides, characterized by various uptake mechanisms, have the potential to extend the residence time and bioavailability of encapsulated drugs. Additionally, bioactive molecules with neurotropic or neuroprotective properties can be delivered to potentially mediate the ND targeting pathways, e.g., neurotrophin deficiency, impaired lipid metabolism, mitochondrial dysfunction, endoplasmic reticulum stress, accumulation of misfolded proteins or peptide fragments, toxic protein aggregates, oxidative stress damage, and neuroinflammation. This review discusses recent advancements in lipid nanoparticles and CPPs in view of the integration of these two approaches into nanomedicine development and dual-targeted nanoparticulate systems for brain delivery in neurodegenerative disorders.