NOVEL APPROACHES FOR BRAIN TARGETING DRUG DELIVERY SYSTEM THROUGH NASAL ROUTE

Prashant Purohit* and Mohit Sharma

The increasing incidence of central nervous system (CNS) disorders such as Alzheimer's disease, Parkinson's disease, stroke, and brain tumors has underscored the urgent need for effective drug delivery strategies that can bypass the blood–brain barrier (BBB). Intranasal drug administration has emerged as a promising non-invasive approach for brain-targeted delivery due to its potential to bypass the BBB. This review explores the major anatomical pathways for nasal-to-brain drug transport—namely, the olfactory nerve, olfactory mucosal epithelium, trigeminal nerve, and systemic circulation. It also discusses key physiological, physicochemical, and formulation-related factors that influence nasal drug absorption and CNS targeting. In addition, strategies to enhance drug delivery through biomaterials such as chitosan, cyclodextrins, penetration enhancers, and new delivery systems (e.g., nanoparticles, liposomes, gels, and microspheres) are detailed. Common experimental techniques for evaluating intranasal drug delivery, including pharmacokinetic, pharmacodynamic, and radiolabeling methods, are reviewed. Despite its potential, challenges such as low targeting efficiency, physiological variability, and interspecies differences limit its clinical application. Continued research is necessary to optimize delivery systems, improve targeting precision, and ensure safety and efficacy in clinical settings. This review highlights literatures regarding pathways and mechanisms of therapeutic agents transporting across nasal mucosa and latest developments on novel DDSs using various formulation strategies to improve the IN drug delivery to brain.