Nose-to-Brain Drug Delivery Systems: Current Advances, Challenges, and Future Perspectives

Abstract

Nose-to-brain drug delivery is an emerging method for improving the delivery of therapeutic agents to the central nervous system (CNS) by using the nasal cavity as a direct route to the brain. Conventional methods of systemic drug delivery often face challenges due to the blood-brain barrier (BBB), which limits the entry of many therapeutic agents into the brain. Intranasal administration, however, offers an alternative by utilizing the olfactory and trigeminal pathways for drug transport, thereby minimizing reliance on the systemic circulation. Recent developments in formulation science and nanotechnology have led to the creation of various nanocarrier systems, such as polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, liposomes, dendrimers, nanoemulsions, and nanogels. These systems help enhance drug protection, solubility, residence time, controlled release, and targeted delivery to the brain. This review provides an overview of nasal anatomy, the limitations posed by the BBB, transport mechanisms, formulation strategies, nanotechnology-based delivery systems, delivery devices, and therapeutic applications. It also addresses current advancements, challenges, and future directions, with a focus on improving the safety, reproducibility, brain exposure, and clinical application of nose-to-brain delivery systems.