Intranasal Delivery of Curcumin-Loaded Pure Drug Self-Assembled Lipid-Based Nanoparticles for Targeted Therapy of Depression

Purpose: Current antidepressants are limited by insufficient efficacy of conventional monoaminergic drugs and poor brain penetration across the blood-brain barrier. This study designed pure curcumin loaded lipid nanoparticle (CNP) with optimized brain-targeting delivery for depression therapy. Methods: Cur molecules first self-assembled into carrier-free drug nanoparticles. Subsequently, CNP were then prepared via thin-film dispersion and fully characterized in terms of particle size, PDI, DSC, XRD, TEM. The antidepressant effect of CNP was systematically investigated via in vitro and in vivo assays, including cellular uptake, LPS-induced stress model in BV2 cells, and in vivo CUMS depression model. Results: CNP displayed uniform spherical morphology with an average size of 115.8 ± 18.3 nm, PDI of 0.216 ± 0.015 and zeta potential of − 27.1 mV, along with high encapsulation efficiency (86.11 ± 4.28%), drug loading (6.62 ± 0.45%) and sustained release behavior. The cellular uptake efficiency of the CNP group reached 41.47 ± 1.45%, which was more than double that of the Cur group (17.21 ± 0.54%). In vitro studies showed that CNP not only rescued the viability of cells damaged by corticosterone and hydrogen peroxide but also exerted significantly enhanced anti-inflammatory and antioxidant effects in lipopolysaccharide induced cellular stress models. In vivo studies indicated that CNP alleviated depressive-like behaviors more effectively. Conclusion: CNP exhibits significantly enhanced antidepressant efficacy, thus providing a promising approach for developing brain-targeted therapeutics for MDD.