Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Ultrason Sonochem. 2011 Sep;18(5):1165-71. doi: 10.1016/j.ultsonch.2011.03.018. Epub 2011 Apr 1.
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.
为了克服阿霉素全身给药引起的副作用，采用纳米聚合物胶束与双频超声辐照联合使用。这些胶束由于声空化而释放药物，而双频超声场会增强这种释放。为了形成载药胶束，使用了 Pluronic P-105 共聚物，将阿霉素物理载入平均粒径为 14nm 的稳定胶束中。在这项研究中，成年雌性 Balb/C 小鼠被移植自发的乳腺癌肿瘤，并以三种形式之一注射 1.3mg/kg 的阿霉素：游离阿霉素、未超声的胶束阿霉素和超声的胶束阿霉素。为了增加空化产率，在 3MHz（I(SATA)=2W/cm(2)）和 28kHz（I(SATA)=0.04W/cm(2)）的同时频率下对肿瘤区域进行了 2.5 分钟的超声处理。注射后 24 小时处死动物，分离并匀浆其肿瘤、心脏、脾脏、肝脏、肾脏和血浆。使用组织荧光法（350nm 激发和 560nm 发射）测定组织中的药物含量，并为每个组织获得标准药物剂量曲线。结果表明，在接受超声处理的胶束阿霉素组中，肿瘤组织中的药物浓度明显高于游离阿霉素注射组（8.69 倍）和未超声的胶束阿霉素组（2.60 倍）。与游离阿霉素（3.35 倍）和未超声的胶束药物（2.48 倍）组相比，超声处理的胶束阿霉素组在其他组织中的药物浓度明显降低（p<0.05）。我们得出结论，双频超声增强了胶束的药物释放，并通过声孔作用增加了肿瘤对药物的摄取。所提出的药物输送系统在提高治疗能力的同时，降低了药物在其他组织中的摄取引起的全身副作用。
