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

Area of Science:

• Neuroscience
• Pharmacology
• Biomedical Engineering

Background:

• Targeting the brain via intranasal drug delivery requires precise deposition at the olfactory cleft.
• Conventional nasal sprays lack the accuracy for effective olfactory cleft drug delivery.

Purpose of the Study:

• To introduce and validate a laminar fluid ejection (LFE) method for precise intranasal drug delivery to the olfactory cleft.
• To assess the efficacy of LFE for brain-targeted pharmaceutical delivery in humans.

Main Methods:

• Utilized a 3D-printed nasal model to optimize LFE parameters (velocity, angle).
• Conducted in-vivo human imaging studies using radiolabeled tracers (Technetium-99) and dyes (methylene blue) to confirm olfactory deposition.
• Employed functional MRI (fMRI) to compare LFE with conventional nasal sprays during insulin delivery.

Main Results:

• LFE demonstrated successful focal deposition at the olfactory cleft using Technetium-99 and methylene blue.
• fMRI showed qualitative decreases in prefrontal cortex activity after insulin delivery via LFE, suggesting brain access.
• LFE showed improved targeted delivery compared to conventional nasal spray.

Conclusions:

• The laminar fluid ejection (LFE) method provides a targeted approach for intranasal drug delivery to the olfactory cleft.
• LFE shows promise for enhancing brain-targeted pharmaceutical delivery, offering an alternative to conventional methods.