Advances in Intranasal Delivery of Exosomes for Central Nervous System Disorders.

Central nervous system disorders are major global health challenges that contribute to significant morbidity and mortality. Traditional therapeutic strategies often face substantial limitations, primarily due to the blood-brain barrier, which restricts the delivery of pharmacological agents to the brain and consequently affects treatment effectiveness. In recent years, in order to enhance the efficacy of the central nervous system treatments, exosome-based approaches have gained interest. Exosomes, small extracellular vesicles (30-150 nm) secreted by cells, present a feasible therapeutic strategy due to their ability to cross the blood-brain barrier and transport bioactive molecules. Reflecting the traits of their parent cells (e.g., glioma stem cells and glioblastoma multiforme), exosomes can be isolated from body fluids, which enhances their clinical applicability. Additionally, intranasal delivery provides a non-invasive method to administer exosomes, using the olfactory and trigeminal nerve pathways to bypass the blood-brain barrier and directly target the brain. This method shows great promise in enhancing therapeutic efficacy for CNS disorders. However, challenges such as rapid mucociliary clearance, enzymatic degradation, and limited bioavailability reduce efficacy. Advances in exosome engineering, nanocarrier systems, and novel delivery devices are under investigation to mitigate these constraints. However, clinical translation requires further research to guarantee safety, consistency, and scalability. In this context, intranasal exosome delivery holds considerable promise as a non-invasive strategy for central nervous system disorder treatment, contingent on overcoming the current biological and technical barriers.