Lavender Oil-Infused Mirtazapine Nanoemulsion for Direct Nose- to-Brain Targeting

Abstract Neurological disorders, such as depression, are difficult to manage owing to limited brain drug delivery and suboptimal therapies. This study developed and evaluated lavender oil-based mirtazapine-loaded nanoemulsions for direct nose-to-brain targeting to enhance therapeutic efficiency and reduce systemic side effects. Nanoemulsions were prepared using homogenization-sonication, incorporating lavender oil, Tween-80, Span-80, ethanol, and distilled water. They exhibited spherical, uniformly distributed nanosized globules with nasal pH compatibility (6.14–6.19). Among the formulations, F4 showed optimal results with a zeta potential of –10.4 ± 0.9, ideal viscosity, high drug entrapment, and excellent in-vitro(92.78%) and ex-vivo (93.28%) mucosal penetration. Molecular docking confirmed the stable binding of mirtazapine to the dopamine receptor (PDB ID: 6CM4) via multiple hydrophobic and π-interactions. All formulations demonstrated stability under centrifugation and freeze-thaw conditions. Overall, this study supports mirtazapine nanoemulsions as a promising, non-invasive strategy for central nervous system drug delivery, improving bioavailability while minimizing systemic toxicity.