NOSE-TO-BRAIN DRUG DELIVERY: A REVIEW

The blood-brain barrier (BBB) represents a major challenge in the treatment of neurological disorders by restricting the entry of many therapeutic agents into the central nervous system (CNS). Nose-to-brain drug delivery has emerged as a promising, non-invasive approach to enhance CNS drug delivery by utilizing the olfactory and trigeminal pathways. This route is particularly advantageous for delivering drugs with poor brain penetration, including peptides, proteins, nucleic acids, and other therapeutic molecules. However, its effectiveness is limited by several factors, including mucociliary clearance, enzymatic degradation, short nasal residence time, restricted dose volume, and variable drug deposition. To overcome these limitations, various formulation strategies, including mucoadhesive polymers, permeation enhancers, in situ gels, liposomes, nanoemulsions, polymeric nanoparticles, solid lipid nanoparticles, and dendrimers, have been investigated. These systems may improve drug stability, enhance nasal retention, facilitate absorption, and provide controlled drug release. Nose-to-brain delivery is being explored for the management of several neurological conditions, including Alzheimer's disease, Parkinson's disease, epilepsy, migraine, brain tumors, stroke, and CNS infections. Recent advances in nanotechnology, thermoresponsive formulations, precision nasal delivery devices, and computational approaches have further expanded its potential. Nevertheless, challenges related to formulation safety, reproducible drug deposition, biodistribution, and clinical translation remain. Further pharmacokinetic investigations, long-term safety assessments, and well-designed clinical trials are essential to establish its therapeutic effectiveness. Overall, nose-to-brain drug delivery represents a promising strategy for improving CNS drug targeting and advancing the treatment of neurological disorders.