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 11 MPa. The increased permeability recovered within 2 h. This enhancement was realized with one-shot low-energy shock waves having an acoustic energy of 0.013 mJ/mm². Monitoring the peak pressures in every exposure revealed that the minimum peak pressure required for the enhancement is 2.9 MPa. 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.

Enhancements of epithelial barrier permeability were evaluated by trans-epithelial electrical resistance (TEER) before and after shock wave exposures.

用于药物递送的常用技术之一是暂时增加组织屏障的渗透性。已知诸如超声波和冲击波的声能可调节组织渗透性。最近，发现冲击波可调节大鼠大脑的血脑屏障，而无需注射诸如微泡的造影剂。该发现暗示在没有造影剂的情况下通过冲击波暴露来调节其他组织屏障是可能的。为了检查利用其他组织屏障是否也可能进行调节，我们在这里研究了冲击波是否会调节体外组织屏障模型，该模型由培养在培养插入物上的上皮细胞组成。冲击波在11 MPa的峰值压力下，通过跨上皮电阻（TEER）评估的上皮片的渗透性增加。增加的渗透率在2小时内恢复。这种增强是通过声能为0.013 mJ / mm的单次低能冲击波实现的²。监测每次暴露中的峰值压力表明，增强所需的最小峰值压力为2.9 MPa。这些结果表明，冲击波暴露有可能暂时增加上皮屏障的通透性，从而在没有造影剂的情况下增强药物的递送。

冲击波暴露前后，通过跨上皮电阻（TEER）评估上皮屏障通透性的增强。