To overcome the side effects caused by systemic administration of
doxorubicin, nanosized polymeric
micelles were used in combination with dual frequency ultrasonic irradiation. These
micelles release the
drug due to acoustic cavitation, which is enhanced in dual frequency ultrasonic fields. To form the
drug-loaded
micelles,
Pluronic P-105 copolymer was used, and
doxorubicin was physically loaded into stabilized
micelles with an average size of 14 nm. In this study, adult female Balb/C mice were transplanted with spontaneous breast
adenocarcinoma tumors and were injected with a dose of 1.3 mg/kg
doxorubicin in one of three forms: free
doxorubicin, micellar
doxorubicin without sonication and micellar
doxorubicin with sonication. To increase cavitation yield, the
tumor region was sonicated for 2.5 min at simultaneous frequencies of 3 MHz (I(
SATA)=2 W/cm(2)) and 28 kHz (I(
SATA)=0.04 W/cm(2)). The animals were sacrificed 24h after injection, and their
tumor, heart, spleen, liver, kidneys and plasma were separated and homogenized. The
drug content in the tissues was determined using tissue fluorimetry (350 nm excitation and 560 nm emission), and standard
drug dose curves were obtained for each tissue. The results show that in the group that received micellar
doxorubicin with sonication, the
drug concentration in the
tumor tissue was significantly higher than in the free
doxorubicin injection group (8.69 times) and the micellar
doxorubicin without sonication group (2.60 times). The
drug concentration in other tissues was significantly lower in the micellar
doxorubicin with sonication group relative to the free
doxorubicin (3.35 times) and the micellar
drug without sonication (2.48 times) groups (p<0.05). We conclude that dual frequency sonication improves drug release from
micelles and increases the
drug uptake by
tumors due to sonoporation. The proposed drug delivery system creates an improved treatment capability while reducing systemic side effects caused by
drug uptake in other tissues.