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

药物输送系统（DDS）超声造影剂的研究

基本信息

批准号：
12680850
负责人：
SATO Toshio
金额：
$ 1.15万
依托单位：
Toin University of Yokohama
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12680850/
关键词：
Ultrasonic Contrast Agent Drug Delivery System Targeting Biotinilation Magnetic Microbubble Cavitation Active oxygen Tumor ターゲティング DDS 静電結合磁性体

项目摘要

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

主要研究了(A)和(B)两种方法设计靶向超声造影剂。在方法(A)中，用生物素标记的微泡来定位和表征包被抗生物素的肿瘤表面。在方法(B)中，加入磁铁矿的微泡可以在体外磁铁的帮助下定位于肿瘤。我们证实，这两种方法中的定位微泡都有可能在流动停止的情况下定位特定的目标。我们还利用模拟实际血液流动的血管模型，证实了这些定点微泡有可能在低流速下定位靶点。但是，随着血管模型中流量的增加，靶向能力明显下降。因此，就在我们继续研究克服上述问题的同时，开始了应用声空化的新方法的研究。在…中在产生高温和高压的声空化空间的更远处，水分子分裂成自由基H2O→H^++OH^-，产生羟基OH^-。声空化产生的微气泡也具有良好的散射特性，因为微气泡的声阻抗与周围的组织有很大的不同。研究结果表明，超声图像质量的提高是值得期待的。也就是说，如果在肿瘤附近选择性地产生声空化，我们就可以用超声诊断设备观察到活性氧对癌细胞的破坏过程。在我们的实质性评估之前，我们使用了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估。接下来，我们实验室研究了超声照射对癌细胞增殖的抑制作用。在烧瓶中对培养的小鼠T淋巴瘤(EL-4)癌细胞进行了超声辐照实验。我们证实，暴露后癌细胞数量没有立即发生明显变化，在暴露后24小时内，随着时间的推移，细胞数量的增加受到了显著的抑制。较少