Nanogel-mediated therapeutic delivery across blood-cerebrospinal fluid and blood-spinal cord barriers

Abstract

Nanogels are emerging as promising nanocarriers for delivering therapeutic agents to treat central nervous system (CNS) disorders. Traditional therapeutic approaches for CNS disorders are often hindered by the inability to cross the blood-cerebrospinal fluid barrier (BCSFB) and blood-spinal cord barrier (BSCB), necessitating high and frequent dosages that can lead to off-target effects. Nanogels, however, offer a unique solution by enabling targeted delivery across these barriers with minimal dosages and a controlled-release mechanism, marking a significant advancement in CNS treatment. This narrative review explores the current knowledge and recent advancements in the application of nanogels for CNS disorders. Specifically, it highlights how chitosan-based, polyethylene glycol-based, polypeptide-based, and dextran-based nanogels effectively cross the BCSFB, while macrophage membrane-encapsulated and polyethylene glycol-based nanogels traverse the BSCB. These nanogels are compatible with a range of therapeutic agents, including neural stem cells, metformin, methotrexate, rolipram, oncomodulin, and antagomir-21, targeting CNS disorders like spinal cord injury and intervertebral disc degeneration. Additionally, nanogels can be administered through various routes such as intravenous, intranasal, intrathecal, and intraganglionic methods. Despite these promising developments, further research is necessary to fully elucidate their mechanisms of action and optimize their therapeutic efficacy for clinical applications.