Drug delivery pathways to the central nervous system via the brain glymphatic system circumventing the blood-brain barrier

The blood-brain barrier (BBB) poses daunting challenges in treating diseases associated with the central nervous system (CNS). Recently, the traditional notion of the absence of the lymphatic system in the brain is evolving. The discovery of the glymphatic system in the brain has stimulated tremendous interest in developing new strategies for the treatment of CNS diseases. Leveraging the glymphatic system for CNS drug delivery may pave a new avenue to circumvent the BBB and achieve efficient drug delivery. The review focuses on the glymphatic system of the brain, discussing potential factors affecting its functions and exploring their connections with the meningeal lymphatic system. Finally, the review provides an overview of the drug delivery methods through the glymphatic system to circumvent BBB and regulate brain immunity. These innovative drug delivery methods may significantly improve drug utilization and create new avenues for the treatment of brain diseases. The discovery of the glymphatic system has opened up a pathway for drug delivery to the brain by circumventing the blood-brain barrier, which can effectively improve drug utilization. The methods of drug delivery through the glymphatic system include intrathecal injection, intranasal injection, and delivery through the meningeal lymphatic vessels. The meningeal lymphatic system and glymphatic system provide new developments for the future drug delivery treatment of brain diseases. image