Development and Characterization of Magnoliae Flos Essential-Oil-Loaded Nanoemulsion: A Spatiotemporal Nose-to-Brain Delivery Enhancer for Solution and Gel-Based Pharmaceutical Formulations

<b>Objective:</b> To develop a stable nanoemulsion loaded with <i>Magnoliae Flos</i> essential oil (MEO-NE) and evaluated its potential as an enhancer for nose-to-brain delivery in both solution and gel formulations. <b>Methods:</b> The MEO-NE was prepared using a low-energy emulsification method, with the formulation optimized via single-factor experiments and Box-Behnken design-response surface methodology. The optimized MEO-NE was characterized for particle size, PDI, morphology, and nasal mucosal irritation. Ex vivo histological imaging in rats was performed using hydrophilic sulfo-cyanine7 carboxylic acid and lipophilic coumarin 6 as fluorescent probes to assess distribution and retention in the trigeminal nerve and brain tissues. <b>Results:</b> The optimized MEO-NE exhibited a small particle size (27.96 ± 0.94 nm), low PDI (0.089 ± 0.013), spherical morphology, a stable O/W structure, and no irritation to the nasal mucosa. Ex vivo imaging revealed that MEO-NE significantly enhanced the distribution and retention of both hydrophilic and lipophilic probes in the trigeminal nerve and brain tissues. Moreover, the gel formulation of MEO-NE demonstrated superior brain-targeting efficiency over the solution within 6 h. <b>Conclusions:</b> MEO-NE served as an effective enhancer for nose-to-brain delivery, improving brain uptake of both hydrophilic and lipophilic drugs, and provided an experimental basis for utilizing herbal essential oils in CNS-targeted delivery systems.