Understanding the permeability and delivery of drug across the nasal olfactory region

<p dir="ltr">Intranasal drug administration offers a promising non-invasive drug route for direct drug delivery to the brain that bypasses the blood-brain barrier via olfactory nerve cells in the olfactory region of the nasal cavity that connects to the olfactory bulb of the brain. With the increasing interest in nose-to-brain drug delivery, a deeper understanding on the permeability and transport of various drugs becomes of increasing importance. Current <i>in vitro </i>model of nasal drug delivery studies utilises human nasal epithelial cell line (RPMI 2650), which is not fully representative of the olfactory region due to the lack of nerve cells. Therefore, developing an <i>in vitro </i>model with inclusion of nerve cells will potentially create a model that is more physiologically relevant for nasal drug delivery studies. This study aims to investigate the permeability and transport of 3 different drugs with different physical chemical properties using current <i>in vitro </i>model: Ibuprofen, Levodopa, and Sertraline Hydrochloride (Sertraline HCl). Additionally, a drug uptake study of a neuroblast cell line (BE(2)-M17) for these drugs was also performed as a preliminary work into a potential <i>in vitro </i>co-culture cell model of human nasal epithelial cells with neuronal cells. The result from the drug transport study showed Ibuprofen to have the highest rate of transport across the epithelial cells, followed by Sertraline HCl, and then Levodopa, which correlates with their logP value. In addition, the result from neuroblast drug uptake study showed similar trends with the most hydrophobic drug, Sertraline HCl, having the highest intracellular drug uptake, followed by Ibuprofen and Levodopa that showed minimal drug uptake in both cell lines. Results from this study shows the important role physicochemical properties played in drug transport across nasal cell membrane and the preliminary evaluation in designing an <i>in vitro </i>model that is more representative of the nasal olfactory region.</p>