Acoustically activated delivery of anthracycline drugs to human leukemia (HL-60) cells from pluronic P105 micelles

To minimize adverse side effects of chemotherapy, a micellar drug carrier was investigated that retains hydrophobic drugs and then releases the drug by ultrasonic stimulation. First, the DNA damage induced by Doxorubicin (DOX) delivered to Human leukemia (BL-60) cells from Pluronic P105 micelles with and without the application of ultrasound was investigated. The comet assay was used to quantify the amount of DNA damage. No significant DNA damage was observed when the cells were treated with 0.1, 1 and 10 wt% P105 with or without ultrasound (70 kHz, 1.3 W/cm2) for 1 hour or for up to 3 hours in 10 wt% P105. However, when cells were incubated with 10 μg/ml free DOX for up to 9 hours, DNA damage increased with incubation time (p = 0.0011). Exposure of cells to the same concentration of DOX in the presence of 10 wt% P105 showed no significant DNA damage for up to 9 hours of incubation. However, when ultrasound was applied, a rapid and significant increase in DNA damage was observed (p = 0.0001).; An ultrasonic exposure chamber with real-time fluorescence detection was used to measure acoustically-triggered drug release from Pluronic P105 micelles under continuous wave (CW) or pulsed ultrasound. Drug release was highest at 20 kHz ultrasound and dropped with increasing ultrasound frequency despite much higher power densities. No release was observed at 1 and 3 MHz. The data suggest an important role of transient cavitation in drug release. Release of DOX was higher than that of Ruboxyl (Rb) presumably due to stronger interaction and deeper insertion of Rb into the core of Pluronic micelles. For the same frequency, drug release increased with increasing power density. Drug release was higher at lower Pluronic concentrations, indicating looser packing of Pluronic PPO segments forming micelle cores.; Fluorescence microscopy showed that labeled Pluronic penetrate the cells with and without ultrasound. Data from flow cytometry suggested that the mechanism of drug uptake by the cancer cells did not appear to be related to endocytosis.; Several physical models and their corresponding mathematics were analyzed to see which if any fit the data. The zero order release with first order re-encapsulation appears to represent this polymeric system better than the other models.; This study indicated that the combination of DOX, ultrasound and Pluronic P105 can be used for controlled drug delivery.