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S. Sonoda, E. Uchino, T. Yamashita, T. Sakamoto, K. Tachibana; Inhibition of Melanoma by Ultrasound-Microbubble-Aided Drug Delivery Suggests Membrane Permeabilization. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5799.
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Ultrasound irradiation-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.
In the in vitro study, the inhibitory effect of bleomycin on the growth of B-16 cells was significantly enhanced after ultrasound irradiation alone and when ultrasound irradiation was combined with MB administration. In the in vivo study, 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.
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