Real-time quantitative monitoring of in vitro nasal drug delivery by a nasal epithelial mucosa-on-a-chip model

ABSTRACT

Objectives

A human nasal epithelial mucosa (NEM) on-a-chip is developed integrated with a novel carbon nanofibers-modified carbon electrode for real-time quantitative monitoring of in vitro nasal drug delivery. The integration of platinum electrodes in the chip also enables real-time measurement of transepithelial electrical resistance (TEER).

Methods

The air-liquid interface culture of nasal epithelial RPMI 2650 cells in the NEM-on-a-chip was optimized to mimic the key functional characteristics of the human nasal mucosa. The epithelial transport of ibuprofen in the NEM-on-a-chip was electrochemically monitored in real-time under static and physiologically realistic dynamic flow conditions.

Results

The NEM-on-a-chip mimics the mucus production and nasal epithelial barrier function of the human nasal mucosa. The real-time drug quantification by the NEM-on-a-chip was validated versus the high-performance liquid chromatography method. The drug transport rate monitored in the NEM-on-a-chip was influenced by the flow in the bottom compartment of the chip, highlighting the importance of emulating the dynamic in vivo condition for nasal drug transport studies.

Conclusion

This novel NEM-on-a-chip can be a low-cost and time-efficient alternative to the costly laborious conventional techniques for in vitro nasal drug transport assays. Importantly, its dynamic microenvironment enables conducting nasal drug transport tests under physiologically relevant dynamic conditions.

KEYWORDS:

• Nasal epithelial mucosa-on-a-chip
• RPMI 2650
• nasal drug delivery
• TEER
• real-time drug screening

Acknowledgments

H Gholizadeh acknowledges the Australian Government Research Training Program (RTP) Scholarship to support her PhD study.

Author contributions

The project was conceptualized by Shaokoon Cheng, Hui Xin Ong, Agisilaos Kourmatzis, and Hanieh Gholizadeh. Experiments conduction and data analysis were performed by Hanieh Gholizadeh with advice and supervision by all co-authors. The manuscript was written by the first author with review and edit from all co-authors.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

H Gholizadeh is the recipient of International Research Training Program Scholarship at Macquarie University, Australia.