Study on ultrasonic cqntrast agent for Drug Delivery System (DDS)

基本研究了(a)和(b)两种方法来设计定位超声造影剂。在方法(a)中，使用生物素标记的微泡来定位和表征亲和素包被的肿瘤表面。在方法(b)中，在体外磁铁的帮助下，结合了磁铁矿的微泡可以定位到肿瘤上。我们证实，在两种方法中，定位微泡都有可能在流体停止的情况下定位特定的目标。我们还通过模拟实际血液流动的血管模型证实，这些定位微泡具有在慢流速下定位目标的潜力。但是，在血管模型中，随着血流的增加，靶向能力明显下降。因此，我们在继续研究克服上述问题的同时，也开始了利用声空化的新方法的研究。在产生高温高压的声空化空间的另一侧，水分子分裂成自由基H2O→H^+ + OH^-，生成羟基自由基OH^-。由于声空化产生的微泡的声阻抗与周围组织有很大的差异，因此微泡具有优异的散射特性。从而提高超声图像的质量。即在肿瘤附近选择性地产生声空化，利用超声诊断设备就可以观察到癌细胞被活性氧破坏的过程。在进行实质性评价之前，我们利用ESR（电子自旋共振装置）对声空化发生器产生的OH自由基进行了定性评价。接下来，我们在实验室研究了超声照射对癌细胞增殖的抑制作用。在烧瓶中对小鼠T淋巴瘤癌细胞（EL-4）进行了超声暴露实验。我们证实，暴露后癌细胞的数量没有立即发生显著变化，并且在暴露后24小时内随着时间的推移，细胞数量的增加受到显著抑制。少

Two method of (a) and (b) were basically investigated to design site-targeted ultrasonic contrast agent. In method (a), a microbubble tagged with biotin is used to localize and characterize an avidin-coated surface of tumor. In method (b), a magnetite incorporated microbubble can be localized to tumor with the aid of an extracorporeal magnet. We confirmed that site-targeted microbubble in all of both methods had the potential to localize the particular target under the condition where the flow is stopping. We also confirmed that these site-targeted microbubbles had the potential to localize the target under slow flowrate by using the blood vessel model that was made to imitate the flow of actual blood. But, it became clear that the targeting ability decreased remarkably with increasing the flowrate in the blood vessel model. Therefore, while we were continuing to study to overcome the problems mentioned above, the study of the new method applying the acoustic cavitation was started. In … More side the space of acoustic cavitation where high temperature and high pressure are generated, a water molecule splits into radicals H2O → H^+ + OH^- producing hydroxyl radical OH^-. Microbubbles produced by the acoustic cavitation had also excellent characteristic of scattering, because acoustic impedance of microbubbles were quite difference from Surrounding organization. As the result, improvement of quality of ultrasonic image is expected. Namely, if the acoustic cavitation is generated near tumor selectively, We will be able to observe the process of the ruin of cancer cell by active oxygen with ultrasonic diagnostic equipment. Prior to our substantial evaluation, we used an ESR (electron spin resonance device) to make a qualitative evaluation of OH radicals produced by the acoustic cavitation generator. Next, suppression of proliferation of cancer cells with ultrasound exposure was studied in our laboratory. An ultrasound exposure experiment was performed on a culture of cancer cells of mouse T lymphoma (EL-4) in a flask. We confirmed that the number of cancer cells did not change remarkably immediately after exposure and increase the number of cells was suppressed remakably with the lapse of time during 24 hours after exposure. Less