Development, Characterization, and Evaluation of the Antidepressant Potential of Crocus sativus SLN Nasal Spray in a Drosophila melanogaster Model.

Abstract

Objective: The objective of this study is to develop and characterize a Crocus sativus (saffron)-based solid lipid nanoparticle (SLN) nasal spray for treating depression by enabling direct nose-to-brain delivery and evaluating its antidepressant potential in a Drosophila melanogaster model.

Materials and methods: Phytochemical screening, antioxidant assays, and HPLC quantification of picrocrocin were performed on Crocus sativus extract. The SLN-based nasal spray was formulated and characterized for particle size, zeta potential, polydispersity index (PDI), drug entrapment efficiency, in vitro drug release, and stability over 4 weeks. The antidepressant efficacy was assessed via a climbing assay in Drosophila melanogaster.

Results: Phytochemical analysis revealed phenolic content (11-36 μg GAE/mg), flavonoid content (43-56 μg QE/mg), and carotenoid content (1.9-30 μg βC/mg). HPLC analysis quantified picrocrocin at 6.3 mg/g, confirming its presence. The SLNs exhibited a particle size of 110-225 nm, a zeta potential of -1 to -0.8 mV, a PDI of 1, and a drug entrapment efficiency of 99.76%. Drug release reached 37% over 270 minutes, and the nasal spray maintained a pH of 5.8, a viscosity of 23.1 cP, and stability over 4 weeks. In vivo, the climbing assay demonstrated improved locomotor activity, indicating significant antidepressant potential.

Conclusion: The Crocus sativus SLN nasal spray exhibits high entrapment efficiency, stability, and promising in vivo antidepressant effects, supporting its potential as a novel therapy for treatment-resistant depression via direct nose-to-brain delivery.