A Review on Recent Advances, Formulation Strategies and Translational Challenges in Nasal Drug Delivery for Brain Targeting

Delivery of therapeutics to the central nervous system (CNS) remains difficult because the blood–brain barrier restricts the entry of many pharmacologically active molecules. Intranasal administration has attracted attention as a non-invasive approach that may increase CNS exposure by exploiting anatomical connections between the nasal cavity and the brain. Drug movement can involve the olfactory region and trigeminal pathways, together with systemic absorption followed by limited passage across the blood–brain barrier. However, successful nose-to-brain delivery is not simply a consequence of placing a drug in the nose. Nasal mucus, mucociliary clearance, enzymatic degradation, limited dose volume, epithelial permeability, formulation instability and variability in nasal anatomy can markedly influence performance. Recent formulation research therefore combines mucoadhesive or mucus-penetrating systems with nanoparticles, liposomes, nanoemulsions, nanogels, in-situ gels, nasal powders and surface-engineered carriers. This review discusses the biological basis of nose-to-brain delivery, major formulation strategies, critical quality attributes, experimental evaluation, therapeutic applications and barriers to clinical translation. Particular attention is given to how formulation design can be connected with residence time, deposition site, drug release and brain exposure. The review also identifies future opportunities in personalized nasal delivery, smart responsive systems, scalable manufacturing and clinically meaningful pharmacokinetic evaluation.