Maximising olfactory deposition of a valproic acid (VPA)-loaded nanostructured lipid carriers (NLC) formulation.

This study aimed to optimise key parameters for maximising olfactory deposition (OD) of a valproic acid (VPA)-loaded nanostructured lipid carriers (NLC) formulation, with particular focus on nasal device selection. Three nasal devices (unidose liquid nasal spray system - UDSl, VP7 pump equipped with a nose-to-brain actuator - VP7N2B, and Preloaded) were tested using two distinct 3D-printed nasal casts and varying administration positions. Among the tested devices, the Preloaded exhibited a narrow spray pattern with consistent delivery, achieving over 50 % OD. This makes it the most promising for nose-to-brain transport, surpassing OD values typically reported in the literature for both powder and liquid formulations, which rarely reach 50 %. Maximising OD required positioning the Preloaded device at a high angle to the horizontal plane (53°), a low angle to the vertical plane (5°), and a deeper insertion depth (ID) (15 mm). While the Preloaded device showed consistent OD across both models, greater variability was observed with UDSl and VP7N2B, likely due to anatomical differences between the nasal casts. These findings highlight the crucial role of nasal device design, spray characteristics, user-independent administration, and positioning in optimising OD. Although this work does not establish a universal in vitro testing method, it lays important groundwork and introduces experimental strategies that could guide future optimisation of NLC-based nasal drug delivery systems.