Abstract
Since the 1980s, there continues to be reports investigating potential routes for the delivery of compounds to the brain after instillation in the nasal cavity. The exact mechanism(s) by which compound translocation from the nose to the brain occurs are unknown. Several hypothesized pathways for compound transport have been proposed and include movement through various nerves in the nasal cavity, the nasal vasculature, or the nasal lymphatic system. However, intercellular transport of large volumes of intranasally instilled inoculum between nasal epithelial cells has been recently reported in hamsters. Intercellular transport in the nose could potentially be used for the non-invasive delivery of drugs to the brain. This thesis looks at the possibility of intercellular transport across the nasal mucosa for the purpose of drug delivery to the brain. |Two liquids were formulated that contained a visual probe suspended in either crude brain homogenate (BH) or a dilute polymer solution. Visual probe suspensions were characterized for the particle size distribution of the visual probe, suspension viscosity, and surface tension. Suspensions were instilled into the noses of hamsters and compared for intercellular transport and biodistribution of the visual probe. Visual probe transport was evaluated in animal groups at 15 and 30 min after inhalation and compared to uninoculated controls and in control animals that received brain homogenate without visual probe. Organs were collected and evaluated for the presence of the visual probe using a validated analytical method using ultra-high pressure chromatography (UPLC). BH-visual probe given to animals that were sacrificed 15 min after inhalation showed intercellular transport between the epithelial cells. BH-curcumin was also found in the lymph vessels of one of the animal that received BH-visual probe suspension and was sacrificed 15 min after inhalation. There was no visual probe detected in any organ 30 min after inhalation of any formulations.