Thara Pannadewi1,2, Jerry Wong1,2, Julie Suman3, Daniela Traini1,2 & Hui Xin Ong1,2
1Woolcock Institute of Medical Research, 2 Innovation Road, Macquarie Park, 2113, NSW, Australia
2Macquarie University, Balaclava Road, Macquarie Park, 2113, NSW, Australia
3Aptar Pharmaceuticals, 26555 Technology Drive, Crystal Lake, Illinois, 60012, USA
Summary
Intranasal (IN) drug delivery offers a promising non-invasive route for targeting the brain bypassing the blood-brain barrier through the olfactory region of the nasal cavity. However, current in vitro models, such as the RPMI 2650 human nasal epithelial cell line, lack neuronal components, limiting their physiological relevance for studying nose-to-brain drug transport. This study investigates the permeability and transport of three drugs—ibuprofen, levodopa, and sertraline hydrochloride (sertraline HCl)—with differing physicochemical properties using the RPMI 2650 model. Additionally, drug uptake was assessed in a neuroblastoma cell line (BE(2)-M17) to explore its potential inclusion in a co-culture model that better mimics the olfactory region.
Results showed that ibuprofen exhibited the highest transport rate across the epithelial monolayer, followed by sertraline HCl and levodopa, which correlated with the drugs’ lipophilicity (logP values). In the neuronal uptake study, sertraline HCl demonstrated the highest intracellular accumulation, while ibuprofen and levodopa showed minimal uptake, suggesting that more hydrophobic drugs were retained within the cell’s intracellular space. These findings highlight the critical role of physicochemical properties in drug transport and uptake across nasal and neuronal cells.
The study underscores the limitations of current nasal models and supports the development of a more physiologically relevant in vitro co-culture system incorporating neuronal cells. Such a model could enhance the predictive accuracy of nose-to-brain drug delivery studies and aid in the design of more effective brain-targeting therapeutics.
04.Pannadewi