Inhibition of melanoma by ultrasound-microbubble-aided drug delivery suggests membrane permeabilization.

Ultrasound exposure-induced cavitation has been shown to accentuate cell membrane permeability, thus promoting effective drug delivery into cells, a technique that can be enhanced in the presence of microbubbles (MB). Here we applied this method as a treatment for malignant melanoma of the eyelid. The incidence of malignant melanoma in ophthalmology is relatively high, but its treatment is cosmetically difficult. A greater in vitro growth suppression of B-16 melanoma cells was achieved using ultrasound and MB in combination with the anticancer drug bleomycin than when a more concentrated dose of bleomycin alone was applied to the cell culture. Moreover, this effect was enhanced in an in vivo tumor model created by injecting B-16 melanoma cells into the lower eyelids of SCID mice. The antitumor effect of bleomycin was observed at a lower dose (0.5 mg/ ml) when the treatment was used in conjunction with ultrasound. The effect was further enhanced when MB were included, with tumor shrinkage occurring at bleomycin levels of 0.06 mg/ml. These results show that ultrasound and MB promote efficient bleomycin uptake by cells, and that the technique is a potentially useful drug delivery method.