Nanomedicine strategies for overcoming the blood–brain barrier in central nervous system drug delivery: mechanisms, advances, and challenges

Central nervous system (CNS) disorders remain one of the most significant challenges in medicine given the restrictive properties of the blood-brain barrier (BBB), which substantially reduces the delivery of most therapeutics to penetrate the brain. Although there has been considerable progress in the generation of support neuroactive substances, approximately 98% of possible CNS medicines never get to effective milligram proofs in the brain, mostly due to exclusion from BBB. This research offers an in-depth and analytical assessment of approaches utilizing nanomedicine aimed at addressing the limitations of the blood-brain barrier (BBB) and improving the delivery of drugs to the brain. It thoroughly explores the structural and functional properties of the BBB, identifies the major obstacles hindering molecular movement, and investigates the cellular and molecular processes that regulate the movement of nanoparticles. Significant focus is given to various nanocarrier platforms, encompassing lipid-based systems (such as liposomes, solid lipid nanoparticles, and nanostructured lipid carriers), polymeric nanoparticles, micelles, dendrimers, nanogels, nanoemulsions, exosomes, carbon nanotubes, and metallic nanoparticles. These platforms are particularly noted for their important functions in improving drug stability, bioavailability, controlled release, and precision targeting within the central nervous system. Furthermore, recent developments in innovative technologies, including nanofiber scaffolds and multidimensional (3D-6D) printing methods for neurological uses, are also discussed. The paper also analyses translational hurdles, safety issues, and toxicity factors that persistently obstruct the clinical application of nanomedicine-based CNS therapeutics. This paper highlights the revolutionary potential of nanotechnology in brain drug delivery and offers insights into future strategies for the rational design of safe and effective nanocarriers to meet unmet demands in CNS disease therapy.