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

Expert Opin Drug Deliv. 2021 Jun;18(6):803-818. doi: 10.1080/17425247.2021.1873274. Epub 2021 Jan 19.

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; TEER; nasal drug delivery; real-time drug screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Epithelial Cells
  • Humans
  • Lab-On-A-Chip Devices*
  • Models, Biological
  • Nasal Mucosa
  • Pharmaceutical Preparations*

Substances

  • Pharmaceutical Preparations