The effect of ultrasound on the cytoxicity of adriamycin

Abstract

The effect of continuous wave ultrasound exposures on the cytotoxicity of adriamycin has been studied. It has been found that 2.6 MHz, 2.3 Wcm-2 (spatial average) ultrasound can enhance the cell killing potential of adriamycin both in suspensions of single V79 chinese hamster fibroblast cells and in spheroids formed from these cells. The ratio of the slopes of the survival curves for single cell suspensions is 1.5. For spheroids, the growth delay is increased by 1.3 days by simultaneous ultrasound exposure. Flow cytometric studies of the intracellular concentration of adriamycin following ultrasound exposure reveals that this is increased when compared with that measured when the cells are only exposed to adriamycin. Evidence is presented to suggest that this is a non-thermal effect of ultrasound.

Ultrasonic drug delivery – a general review

“…Loverock et al have shown that 1 hr of exposure to ultrasound (2.3 W/cm 2 at 2.6 MHz at) rendered Doxorubicin (Dox) significantly more toxic to Chinese hamster lung fibroblasts [150]. Exposure to ultrasound alone did not affect cell viability.…”

Therapeutic ultrasound: Its application in drug delivery

“…As such, ultrasound tends to enhance the chemotoxicity of hydrophobic drugs. Using doxorubicin as a model drug, several investigators have shown that ultrasound enhances cellular uptake of doxorubicin, 29,32,37 suggesting that the site of action of the non-thermal mechanism of ultrasound might be the cell membrane. In such a scheme, the increased rate of penetration of cytotoxic drug underlies the observed enhancement in cytotoxicity.…”

In vitro interaction of lithotripter shock waves and cytotoxic drugs

“…Such a mechanism also allows to explain the dependency of the DERs upon the incubation time. A study on the effect of ultrasound on the cytotoxicity of doxorubicin already demonstrated an increased intracellular drug level after combined treatment (Loverock et al, 1990). Our further studies are aimed at the direct determination of intracellular drug concentration after exposure to shock waves.…”

“…An enhanced effect of a combined application of shock waves and cytotoxic drugs was also demonstrated in tumour cell cultures (Oosterhof et al, 1989;Wilmer et al, 1989;Lee et al, 1990). Recently, it was reported that ultrasound can enhance the cytotoxicity of doxorubicin (Loverock et al, 1990).…”

“…An enhanced effect of a combined application of shock waves and cytotoxic drugs was also demonstrated in tumour cell cultures (Oosterhof et al, 1989;Wilmer et al, 1989;Lee et al, 1990). Recently, it was reported that ultrasound can enhance the cytotoxicity of doxorubicin (Loverock et al, 1990).Only a limited number of cytotoxic drugs has so far been tested in combination with shock waves. In this study the combined effect of shock waves and five cytotoxic drugs, cisplatin, and the anthracylcine antibiotics doxorubicin, daunorubicin, THP-doxorubicin, and aclacinomycin, was investigated in vitro.…”