Breaking the brain barrier: Hybrid nanoparticle-enabled delivery for next-gen neurotherapeutics

Neurological disorders are beholden for mortality, morbidity, and disability. According to the new WHO position paper promulgated on August 9, 2022, “Disorders of the nervous system are the second commanding antecedent of death globally, accounting for 9 million deaths per year”. The physiological structure, components and their function in maintaining the integrity of blood brain barrier (BBB), limits the entry of drugs. Various transport mechanisms are discussed, such as paracellular, transcellular, carrier-mediated transport, adsorptive mediated transport, and receptor-mediated transport. Delivering therapeutics across the BBB while avoiding neurotoxins is the primary challenge in formulating novel pharmaceutical drug delibvery alternatives for the treatment of brain diseases. A strategy based on nanotechnology can improve a drug's pharmacokinetic profile and optimize drug transport. Drug transport in neurodegenerative diseases may be improved by nanoparticle formulations that contain therapeutics that target particular biochemical processes in the brain. Recent advancements in materials science and nanotechnology offer advanced materials with customized properties for targeted drug delivery. Research on the brain and BBB has led to the development of strategies for enhanced BBB crossing. Hybrid nanoparticles serve as a promising drug delivery vehicle which promotes the brain transport of drugs. This review discusses the structure, function, cells, and mechanisms of biotraficking across BBB. An emerging strategy for BBB crossing, a hybrid nanoparticle-based drug delivery system for brain delivery for various brain diseases like Alzheimer's, Parkinson's, Huntington's, Glioblastoma, Epilepsy, Schizophrenia, Traumatic Brain Injury, Migraine, and other neuroinflammatory disease like Krebbs etc are discussed.