Doxorubicin delivery into tumor cells with ultrasound and microbubbles.

Doxorubicin is a potent chemotherapeutic whose severe side effects limit its application. Drug-targeted delivery with noninvasive techniques is required to increase the drug concentration locally and to reduce systemic side effects. Microbubble-assisted ultrasound has become a promising strategy for noninvasive local drug delivery. The aim of this study is to evaluate the applicability and the effectiveness of administration of doxorubicin combined with microbubble-assisted ultrasound in human U-87MG glioblastoma and MDA-MB-231 breast cancer cells. In the present study, the doxorubicin delivery aided by microbubble-assisted ultrasound enhanced the death of breast cancer and glioblastoma cells, including the induction of apoptosis. Various microbubbles were evaluated including Vevo Micromarker, BR14, SonoVue and experimental polymer shelled microbubbles. The results showed that Vevo Micromarker microbubble-assisted ultrasound could induce an enhancement of doxorubicin in glioblastoma and breast cancer cell death. Polylactide-Shelled PEG and Vevo Micromarker microbubbles were the best microbubbles for efficient doxorubicin delivery in the U-87 MG and MDA-MB-231 cells, respectively. Moreover, the induction of apoptosis by doxorubicin and Vevo Micromarker microbubble-assisted ultrasound was examined and results showed a positive increment for acoustic pressures above 600 kPa. The conclusions drawn from in vitro study show the potential of this strategy for an in vivo application.