Development and evaluation of ultrasound therapeutic system for drug activation

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Concerning development and evaluation of ultrasound therapeutic system for drug activation, multi-frequency ultrasonic generator was made. Frequency dependence of cell killing induced by ultrasound, enhancement of transdermal absorption of drugs, enhancement of biological and chemical effects by echo contrast agents and an echo contrast agent mimic, ultrasonic gene transfer and apoptosis induced by ultrasound were investigated.1. The relative ratio of iodine release vs. cell killing of rat thymocytes was the order of frequencies, 0.5 MHz>1.0 MHz>38 kHz>2.0 MHz. Partial protection was observed on the cell killing after sonication with 0.5 MHz in Ar-saturated solution in the presence of a free radical scavenger, cysteamine.2. An echo contrast agent mimic, PVC-AN (poly-vinylidene chloride-acrylonitryl copolymer), enhanced H_2O_2 production induced by ultrasound through the superoxide dependent pathway in air-saturated aqueous solution, although PVC-AN acted as a free radical scavenger to lower H_2O_2 formation by recombination of OH radicals. Enhancement of ultrasonically induced cell lysis and thrombolysis in the presence of PVC-AN was observed.3. Enhancement of transdermal absorption of acetylcholine in rat due to ultrasonic exposure was observed.4. Evidence of enhancement of gene transfer in HeLa cells and apoptosis in U937 cells induced by ultrasound in the presence of an echo contrast agent, Levovist, was also obtained.