Hanieh Gholizadeh1,2, Shaokoon Cheng2, Agisilaos Kourmatzis3, Zara Sheikh1, Daniela Traini1,4, Paul Young1,5 & Hui Xin Ong1,4
1Respiratory Technology, The Woolcock Institute of Medical Research, Sydney, NSW 2037, Australia
2 School of Engineering, Macquarie University, Sydney, NSW 2109, Australia
3School of Aerospace, Mechanical and Mechatronic Engineering, The University of Sydney, Sydney, NSW 2006, Australia
4Department of Biomedical Sciences, Faculty of Medicine, Health, and Human Sciences, Macquarie University, Sydney, NSW 2109, Australia
5 Department of Marketing, Business School, Macquarie University, Sydney, NSW 2109, Australia
Summary
A dual-channel nose-on-a-chip (NOC) was developed incorporating an air-liquid interface model of human nasal epithelial cells as a novel platform for testing nasal drug delivery in-vitro. The novelty of the NOC lies in mimicking realistic deposition of drug aerosols in the apical donor microchannel, where the cells are exposed to a flow-induced shear stress of 0.23 Pa, mimicking the in-vivo nasal airflow during inhalation. In addition, a pulsatile fluid flow within the acceptor basolateral microchannel mimics the systemic circulation through the vasculatures in the human nasal mucosa. This dynamic microenvironment significantly influences the transport profile of ibuprofen (IBU-model drug) across the nasal epithelium. The pulsatile flow in the basolateral microchannel significantly increases the rate of drug transport and the delivery of aerosolized drug under flow conditions in the apical microchannel causes a further increase in the percentage of transported IBU. Furthermore, the barrier function of the nasal epithelium remains unaffected throughout the study, as assessed by the in-situ transepithelial electrical resistance measurements. Hence, this NOC highlights the significant effect of the biomechanical factors such as shear stress on nasal drug delivery assay results and the importance of incorporating these physiological dynamic conditions for in-vitro nasal drug testing. The miniaturized platform of the NOC with in-built electrochemical and impedance sensors is rapid and relatively economical for quantification of IBU transport and epithelial integrity, respectively. Importantly, these sensors are sufficiently accurate for the quantification of the IBU transport and comparable to current analytical methodologies.
Key Message
Nasal drug delivery testing using the physiologically relevant dynamic microenvironment recreated by the NOC demonstrated the impact of biomechanical factors such as shear stress and dynamic real aerosol deposition on drug permeability. Hence, NOC can serve as a potential alternative to the conventional static models and enhance in-vitro in-vivo correlations.