Therapeutic potential of stable cavitation: From enhanced drug delivery to faster hemorrhage control

Abstract

Current studies indicate that mechanical effects of therapeutic ultrasound resulting in a cavitation activity may be advantageous in variety of clinical applications including tumor treatment, treatment of stroke and vascular diseases, targeted gene and drug delivery, and hemorrhage control. Our drug delivery studies using 880 kHz ultrasound have shown that enhancement of drug delivery through the cornea correlated well (R2̂=0.92) with stable cavitation activity. The delivery enhancement ranged from two to ten times and the power of subharmonic ranged form 5 dBm to 20 dBm in the intensity range of 0.2 0.6 W/cm2. Broadband noise, as an indication of inertial cavitation, was also detected at the highest applied intensity. Changes in the front surface layer of the corneal epithelium indicated the presence of both stable and inertial cavitation activity. Our hemostasis studies have shown that introduction of external microbubbles during application of 5.5 MHz high−intensity focused ultrasound (HIFU) led to faster hemorrhage control of solid organ injuries, appearing to result from both stable and inertial cavitation activity at the location of HIFU focus in a bleeding incision. Microbubbles also allowed easier targeting of an incision site under ultrasound guidance, thus facilitating faster localization and sealing of bleeding incisions.