An in vitro model of temporal enhancement of epithelium barrier permeability by low-energy shock waves without contrast agents.

Abstract

One of the commonly used techniques for drug delivery is to temporarily increase the permeability of tissue barriers. Acoustic energies such as ultrasound and shock waves are known to modulate tissue permeability. Recently, it was found that shock waves modulate the blood-brain barrier in the rat brain without injection of contrast agents such as microbubbles. This finding implies that modulation of other tissue barriers by shock wave exposure without contrast agents may be possible. To examine whether the modulation is also possible with other tissue barriers, we here investigated whether shock waves would modulate an in vitro tissue barrier model consisting of epithelial cells cultured on culture inserts. The permeability of the epithelium sheets evaluated by trans-epithelial electrical resistance (TEER) was increased following shock waves at a peak pressure of 11MPa. The increased permeability recovered within 2h. This enhancement was realized with one-shot low-energy shock waves having an acoustic energy of 0.013mJ/mm2. Monitoring the peak pressures in every exposure revealed that the minimum peak pressure required for the enhancement is 2.9MPa. These results indicate that shock wave exposure has the potential to temporarily increase the permeability of epithelium barriers to enhance drug delivery without contrast agents. Graphical abstract Enhancements of epithelial barrier permeability were evaluated by trans-epithelial electrical resistance (TEER) before and after shock wave exposures.