Evaluation of doxorubicin-containing microbubbles for ultrasound-triggered delivery

Doxorubicin (Dox) is a potent chemotherapeutic compound whose severe side effects limit its application. Microbubble-assisted ultrasound has become a promising strategy for non-invasive local drug delivery to increase the drug concentration locally and to reduce systemic side effects. The aim of this study is to evaluate the effectiveness of administration of Dox-liposomes loaded on microbubbles (Dox-LPS MBs) combined with ultrasound in human U-87MG glioblastoma cells. Experiments were carried out with free Dox or Dox-LPS MBs (final concentration of Dox, 3 µg/mL) on a cell suspension of U-87MG cells. Ultrasound waves were transmitted at 1 MHz frequency with a pulse repetition period of 100 µs, 40 cycles per pulse and for 30s. Cell viability was evaluated by Trypan blue assay 24h and 48h later. Using Dox alone, the cell viability was 63±3% and 26±2% at 24h and 48h later, respectively. The combination of ultrasound at 600 kPa and Dox-LPS MBs induced a 2.5-fold decrease of cell viability compared to the incubation of Dox-LPS MBs alone at 24h and 48h after treatment, respectively. At 24h, this combination was 3 times more efficient than the doxorubicin treatment alone. The conclusions drawn from this in-vitro study show the potential of this strategy for a controlled, efficient, and safe drug delivery. Indeed, the encapsulation of doxorubicin into liposomes and the ultrasound-triggered delivery would allow a reduction of therapeutic dose and side effects of doxorubicin.