A Detailed Review on Bridging Niosomal Carriers for Nose to Brain Drug Delivery: Principles, Translational Pathways and Attributes

Non-invasive nasal drug delivery systems have emerged as a promising route for drug administration. It facilitates rapid therapeutic effect, bypass first pass metabolism, increase patient compliance and provides nose-to-brain drug delivery. The nasal mucosa possesses high vascularization and large surface area enabling efficient uptake of both systemic and locally administered drugs. Nasal administration is especially beneficial in emergency situations such as migraines, seizures, and severe pain. Nasal dosage forms have been developed to enhance drug retention and improve therapeutic efficacy. Niosomal carriers offer a versatile and clinically promising platform to overcome the anatomical and physiological barriers of nose-to-brain drug delivery, combining enhanced mucosal adhesion, tunable release kinetics, and improved drug stability to facilitate direct transport along olfactory and trigeminal pathways. This review synthesizes fundamental principles of niosome design, surfactant selection, bilayer composition, size and surface charge modulation, and functionalization strategies to illustrate how physicochemical attributes govern mucociliary clearance, epithelial uptake, and neuronal translocation. Critical attributes such as encapsulation efficiency, payload versatility, stability under nasal conditions, and potential for targeted ligand decoration are evaluated alongside strategies to mitigate immunogenicity and off target deposition. The niosomal systems poised to expand therapeutic options for central nervous system disorders via minimally invasive intranasal administration.