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.
Sonoda
Shozo
S
Department of Ophthalmology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Tachibana
Katsuro
K
Uchino
Eisuke
E
Yamashita
Toshifumi
T
Sakoda
Kenji
K
Sonoda
Koh-Hei
KH
Hisatomi
Toshio
T
Izumi
Yuichi
Y
Sakamoto
Taiji
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D001761:Bleomycin / Q000008:administration & dosage*; D002463:Cell Membrane Permeability; D003911:Dextrans / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods*; D005134:Eye Neoplasms / Q000188:drug therapy*; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000031:analogs & derivatives; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D016513:Mice, SCID; D045423:Microbubbles; D014465:Ultrasonics
D000903:Antibiotics, Antineoplastic; D003911:Dextrans; C015219:fluorescein isothiocyanate dextran; D001761:Bleomycin; D016650:Fluorescein-5-isothiocyanate