It is well known that ultrasound enhances drug delivery to tissues, although there is not a general consensus about the responsible mechanisms. However, it is known that the most important factor associated with ultrasonically-enhanced drug permeance through tissues is cavitation. Here we report results from research conducted using a experimental approach adapted from single bubble sonoluminescence experiments which generates very well defined acoustic fields and allows controlled activation and location of cavitation. The experimental design requires that a biological tissue be immersed inside a highly degassed liquid media to avoid random bubble nucleation. Therefore, live frog bladders were used as the living tissue due to their high resistance to hypoxia. Tissue membrane permeance was measured using radiolabeled urea. The results show that an increase in tissue permeance only occurs when cavitation is present near the tissue membrane. Moreover, confocal microscopy shows a direct correlation between permeance increases and physical damage to the tissue.
A variety of methods have been used to detect and measure the presence and size of bubbles that occur naturally in tubes or blood vessels. These traits have recently produced interest in biomedical fields including drug delivery systems and decompression sickness, among others. To detect and measure bubbles, optical, acoustic, and equivalent bulk properties methods have primarily been used; each exploiting unique characteristics of bubbles [1]. Among these, Doppler techniques based on the backscattering of ultrasound waves, have been used to detect and measure bubbles within fluid media [2,3].
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