Nose-to-Brain Delivery of Chlorella vulgaris Extracellular Vesicles for Antidepressant Effects.

ABSTRACT: Current antidepressants face limitations due to the blood-brain barrier (BBB), systemic side effects and delayed onset. Here, we engineered an intranasal thermosensitive hydrogel (EVs@IN) encapsulating Chlorella vulgaris-derived extracellular vesicles (EVs) for sustained nose-to-brain delivery. EVs@IN significantly enhanced nasal mucosal retention and facilitated targeted transport of EVs to the hippocampus via olfactory pathways, while minimizing pulmonary exposure and clearance. In mouse models of depression (LPS-induced and CUMS), intranasal EVs@IN elicited rapid and potent alleviation of depressive- and anxiety-like behaviours. Mechanistically, EVs modulated astrocyte phenotypic transformation, reducing the release of neurotoxic complement C3 and suppressing neuroinflammation. Concurre

SUBMITTER: Jin K 

PROVIDER: S-EPMC12626165 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature