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Research Paper
Inhibition of Melanoma by Ultrasound-Microbubble-Aided Drug Delivery Suggests Membrane Permeabilization
Shozo Sonoda, Katsuro Tachibana, Eisuke Uchino, Toshifumi Yamashita, Kenji Sakoda, Koh-Hei Sonoda, Toshio Hisatomi, Yuichi Izumi and Taiji Sakamoto
volume 6 | issue 8
August 2007Pages: 1276 - 1283
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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.
Authors
Shozo Sonoda
Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Katsuro Tachibana
Fukuoka University School of Medicine, Fukuoka, Japan
Eisuke Uchino
Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Toshifumi Yamashita
Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Kenji Sakoda
Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Koh-Hei Sonoda
Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Toshio Hisatomi
Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Yuichi Izumi
Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Taiji Sakamoto
Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima, Japan
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.