Nose-To-Brain Drug Delivery: Mechanisms, Influencing Factors, And Formulation Strategies

Central nervous system (CNS) disorders represent a major global health burden and remain difficult to treat due to the restrictive nature of the blood–brain barrier (BBB), which prevents nearly all large molecules and approximately 98% of small molecules from entering the brain in therapeutic concentrations [1–4]. Conventional systemic delivery approaches often fail to achieve effective CNS drug levels while producing systemic side effects. Nose-to-brain (N2B) drug delivery has emerged as a promising, non-invasive alternative that bypasses the BBB by exploiting direct anatomical connections between the nasal cavity and the brain via olfactory and trigeminal pathways [5–7]. This review summarises the anatomical and physiological basis of N2B delivery, mechanisms of drug transport, factors influencing nasal absorption, advanced formulation strategies including nanocarriers and in situ systems, and current challenges affecting clinical translation