Intranasal drug delivery: Unlocking the nose-to-brain route for central nervous system therapies

Intranasal drug delivery is rapidly gaining momentum as a game-changing approach for central nervous system (CNS) therapies, owing to its ability to bypass the blood-brain barrier (BBB) via olfactory and trigeminal pathways. It also enables systemic drug absorption while avoiding the metabolic drawbacks of oral administration, such as hepatic first-pass degradation. Recent advancements in intranasal formulation technologies, including in situ gels, nanoparticle-based systems, and permeation enhancers, have significantly enhanced drug retention, bioavailability, and targeted delivery. In addition, next-generation intranasal drug delivery devices, including bidirectional nasal sprays and the precision olfactory delivery (POD) technology, have further optimised drug deposition efficiency and enhanced therapeutic outcomes. Despite these advancements, several challenges persist, especially rapid mucociliary clearance in the nasal cavity and poor patient adherence, which limit clinical usage of intranasal medications. This review provides a comprehensive analysis of the anatomical considerations in drug absorption, formulation strategies, and technological advancements in intranasal drug delivery devices, emphasising its potential in overcoming traditional drug delivery barriers and unlocking new therapeutic potential for CNS and systemic applications. Future research should prioritise the enhancement of mucoadhesive properties, the optimisation of permeation enhancers, and the development of novel intranasal delivery devices to maximise clinical efficacy.