Overcoming translational barriers in nose-to-brain drug delivery for clinical applications

Recent research has shown an increasing interest in nose-to-brain drug delivery due to its non-invasive nature and ability to transport therapeutics directly to the central nervous system. This approach offers significant advantages over traditional administration routes, such as the circumvention of the blood-brain barrier and avoidance of first-pass metabolism, thereby enhancing therapeutic efficacy while reducing systemic side effects. Despite promising preclinical findings, nose-to-brain delivery remains underrepresented in the pharmaceutical market, highlighting a critical gap between experimental research and clinical translation. This review critically examines the major challenges confronting nose-to-brain delivery systems, including formulation development, selection of nasal devices, and methodologies for evaluating the nasal biopharmaceutics of drugs during nose-to-brain delivery. Furthermore, strategic recommendations and research priorities are outlined to address these barriers. By identifying and analyzing factors that contribute to the translational failure of nose-to-brain drug delivery systems, it is believed that more effective delivery systems can be developed, ultimately revolutionizing treatment strategies for neurological diseases.