Chrono-neuro-nanocarriers: Synchronizing circadian rhythms and glymphatic flow for targeted brain drug delivery

Nevertheless, a variety of physiological barriers, including the blood–brain barrier (BBB), along with dynamic neurobiological processes that vary across the circadian cycle, continue to restrict effective drug transport to the central nervous system (CNS). Although chronotherapy and nanocarrier-based strategies have independently improved aspects of CNS pharmacology, it remains insufficiently defined how these approaches can be coherently aligned with emerging insights into glymphatic physiology. This study explores the potential combined effects of circadian biology, glymphatic dynamics, and nanocarrier-based tactics on the distribution and clearance of drugs across the central nervous system after the blood-brain barrier (BBB). Instead of suggesting a novel delivery method, the review critically summarizes the body of research to assess how temporal physiology may influence intraparenchymal drug exposure in accordance with accepted BBB-crossing strategies. Using a systems-level approach, this study identifies translational limitations, highlights guiding concepts, and suggests future avenues of inquiry for temporally guided CNS drug delivery.