Nanocarriers for Brain Targeting: Overcoming the Blood-Brain Barrier in Neuropharmacology

The blood-brain barrier (BBB) is a highly selective physiological barrier that protects the central nervous system from harmful substances while maintaining brain homeostasis. However, the BBB significantly limits the delivery of therapeutic agents to the brain, creating major challenges in the treatment of neurological disorders. Conventional drug delivery systems often fail to achieve sufficient drug concentrations in brain tissues due to poor permeability, enzymatic degradation, and systemic elimination. Nanocarrier-based drug delivery systems have emerged as a promising strategy to overcome BBB-related limitations and improve targeted brain delivery. Nanocarriers such as liposomes, polymeric nanoparticles, dendrimers, solid lipid nanoparticles, nanoemulsions, metallic nanoparticles, and polymeric micelles offer enhanced drug stability, improved bioavailability, prolonged circulation time, controlled drug release, and targeted delivery to diseased brain tissues. These systems can cross the BBB through receptor-mediated transcytosis, adsorptive-mediated transcytosis, carrier-mediated transport, and temporary BBB modulation. Surface modification with ligands, peptides, antibodies, and polymers further enhances targeting efficiency and therapeutic outcomes. Nanocarrier-based approaches have shown promising applications in Alzheimer’s disease, Parkinson’s disease, epilepsy, stroke, multiple sclerosis, and brain tumours. Despite substantial progress, challenges related to toxicity, immunogenicity, scalability, regulatory approval, and long-term safety remain significant concerns. This review discusses the structure and functions of the BBB, mechanisms of nanocarrier transport across the BBB, different classes of nanocarriers, therapeutic applications in neuropharmacology, recent advancements, current limitations, and future perspectives in brain-targeted nanomedicine.