May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Inhibition of Melanoma by Ultrasound-Microbubble-Aided Drug Delivery Suggests Membrane Permeabilization
Author Affiliations & Notes
  • S. Sonoda
    Department of Ophthmalogy, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
  • E. Uchino
    Department of Ophthmalogy, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
  • T. Yamashita
    Department of Ophthmalogy, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
  • T. Sakamoto
    Department of Ophthmalogy, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
  • K. Tachibana
    Department of Anatomy, Fukuoka University School of Medicine, Fukuoka, Japan
  • Footnotes
    Commercial Relationships S. Sonoda, None; E. Uchino, None; T. Yamashita, None; T. Sakamoto, None; K. Tachibana, None.
  • Footnotes
    Support Grants-in-Aid for Scientific Research from Ministry of Education, Science and Culture of Japanese Goverment 17659550
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 5799. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: 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.

Methods:: 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.

Results:: 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.

Conclusions:: These results show that ultrasound and MB promote efficient bleomycin uptake by cells, and that the technique is a potentially useful drug delivery method.

Keywords: melanoma • drug toxicity/drug effects 
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