Laminar Fluid Ejection for Olfactory Drug Delivery: A Proof of Concept Study.

Focal intranasal drug delivery to the olfactory cleft is a promising avenue for pharmaceuticals targeting the brain. However, traditional nasal sprays often fail to deliver enough medication to this specific area. We present a laminar fluid ejection (LFE) method for precise delivery of medications to the olfactory cleft. Using a 3D-printed model of the nasal passages, we determined the precise velocity and angle of insertion needed to deposit fluid at the olfactory cleft. Then, we conducted three proof-of-concept in-vivo imaging studies to confirm olfactory delivery in humans. First, we used Technetium-99 (a radiolabeled tracer) and methylene blue (a laboratory-made dye) to visualize olfactory deposition. Both tracers showed successful deposition. In a separate study, we used functional MRI (fMRI), to compare our LFE method with a conventional nasal spray while delivering insulin. From the fMRI results, we qualitatively observed focal decreases in brain activity in prefrontal cortex following insulin delivery. Overall, these preliminary results suggest that LFE offers a targeted approach to olfactory drug delivery, opening opportunities for access to the brain.Clinical and Translational Impact Statement - Focal deposition at the olfactory cleft is a promising target for delivering medication to the brain. We present in-human tests of a laminar fluid ejection method for intranasal drug delivery and demonstrate improvements over conventional nasal spray.