Enhanced Cellular Permeation Efficiency Through Mechanical Vibration-induced Actin Cytoskeleton Changes in Human Nasal Epithelial Cells

초록

Drug delivery through the intranasal route has several advantages. The intranasal route provides higher bioavailability than oral administration, and it can bypass liver digestion of the drug, which is expected in the case of oral administration. However, there are some disadvantages in intranasal drug delivery: Drug residence time in the nasal cavity is short, and the permeation efficiency through the nasal epithelium is unsatisfactory. Several strategies to enhance intranasal permeation efficiency or increase retention time have been studied. Previous studies indicated that mechanical stresses could enhance paracellular permeability. In this study, we exposed human nasal epithelial cells to mechanical vibrations (0.6 x g, 38 Hz) to increase cellular permeability. There was no significant decrease in cell viability under all mechanical vibration conditions tested. Transepithelial electrical resistance (TEER) decreased by approximately 35% and paracellular permeability of fluorescein sodium salt (MW 376Da; NaFI) increased by about 15% following exposure of human nasal epithelial cells to mechanical vibration (20 min, 0.6 x g). Gene expressions of tight junction and adherens junctions were not significantly changed. The ratio of G-actin to F-actin was analyzed to assess changes in the cytoskeletal structure under mechanical vibration. Following exposure of cells to mechanical vibration, the G-actin to F-actin cytoskeletal ratio increased 2.3-fold compared to the control cells.

키워드