Intranasal delivery of curcumin via biomimetic microglial membrane-coated chitosan nanoparticles alleviates depressive-like behaviors in LPS models

Accumulating evidence has shown that chronic neuroinflammation underlies the pathogenesis of major depressive disorder, and anti-inflammatory strategies represent a promising therapeutic direction. Curcumin (Cur), a natural compound with antidepressant, anti-inflammatory, and neuroprotective properties, has emerged as a candidate for depression treatment. However, its clinical translation is limited by poor bioavailability and inefficient delivery across the blood–brain barrier. Here, we developed a responsive biomimetic nanomedicine system for enhanced delivery of curcumin. Phenylboronic acid-modified chitosan nanoparticles were used to encapsulate Cur with high loading efficiency and stimulus-responsive release properties. These cores were further coated with microglia-derived membranes to form biomimetic nanomedicine (mCBC). mCBC demonstrated good biocompatibility and was efficiently internalized by target cells. Following intranasal administration, mCBC significantly reduced neuroinflammation and attenuated neuronal damage in a lipopolysaccharide (LPS)-induced model of depression. These neuroprotective effects were associated with the amelioration of anhedonia and depressive-like behaviors in LPS models, suggesting that mCBC treatment is a promising nanotherapeutic strategy for inflammation-related depression.