Elucidation of Disintegration Mechanism of Microcapsules including a Gas Bubble and Nano-particles for Drug Delivery in Blood Flows Using Underwater Shock Waves

本研究的目的是探讨这一机制，并将冲击波技术应用于生物过程工业和医疗领域，如药物输送系统（DDS）。在本项目中，特别地，研究了以下应用于DDS的重要事项：（A-1）冲击波DDS中的动脉壁和血栓附近的胶囊和细胞的刺激。(A-2)关于这些主题的结果获得如下：（A-1）在内皮细胞的情况下，冲击波对细胞的刺激增加了细胞数量的生长速率。虽然该结果显示了降低抗癌效果的可能性，但是可以优化两个参数，例如崩解和细胞生长，因为生长速率取决于压力波（冲击波）的上升频率和振幅（A-2）。为了将冲击波传播的理论模型应用于细胞， ...更多信息 细胞模型由周围流体、细胞膜和内部流体三种结构组成。利用这些模型，分析了水下冲击波作用于电池时，电池内部和薄膜上的应力和压力波。其结果是，上升频率越高，单元上的应力波越大。为了进一步发展冲击波的产生方法，本论文从以下两个方面进行了研究：（B-1）激光冲击波的产生（B-2）气泡微胶囊的制备及其力学性能的测定。（B-1）确立了使用Yag激光器的冲击波产生方法，但是在光纤和透镜之间的光学耦合部分中的能量损失高，并且冲击波产生的稳定性不好。因此，改变了在试验水池中引入冲击波的方法，将激光束直接照射到水池系统中。(B-2)可以得到由气泡、液体、囊膜组成的特殊微胶囊，其粒径为20-30 μm。该尺寸是2003年之前研究的30%，发现该尺寸适合用作人体内的膀胱DDS。少

In this study, our aim is to investigate this mechanism and apply the shock wave technology to disintegrate cell in the bioprocess industry and medical field such as Drug Delivery Systems (DDS). In this project, especially, the following important things for applying to DDS were investigated(A-1) Stimulus of the capsule and the cell near the arterial wall and thrombus in the shock wave DDS.(A-2) Establishment of disintegration of microcapsule and stimulus of the cell by shock waveThe results about these topics are obtained as follows;(A-1) The stimulus of shock waves on the cell increases the growth rate of the cell number in case of endothelial cells. Although this result shows possibility of decreasing the effects of anti-cancer, it is possible to optimize two parameters such as disintegration and cell-growth because the growth rate is dependent on the rise frequency and amplitude of pressure wave (shock wave)(A-2) To apply theoretical model of the shock wave propagation to the cell, … More the cell model was composed of three structures such as the surrounding fluid, cell membrane and internal fluid. Using these models, the stress and pressure wave on the membrane and in the cell were analyzed in case of working underwater shock wave on the cell. As a result, the higher the rising frequency becomes high, the larger the stress wave on the cell increases. Then it was found that the effect of frequency on the stimulus is high.For the development of generating shock wave method, the following two things are investigated as the actual application;(B-1) Generation of shock wave using Laser(B-2) Development of small scale microcapsule including a gas bubble and measurement of their mechanical properties.The results about these topics are obtained as follows;(B-1) The generation method of shock wave using Yag Laser was established, but energy loss in the part of optical coupling between optical fiber and lens is high and the stability of shock wave generation was not good. So the method to introduce the shock wave in the test water tank will be changed, then the laser beam will be directly to the water tank system.(B-2) The special microcapsules composed of gas bubble, liquid, capsule membrane can be obtained, and the diameter size of them is 20-30 μm. This size is 30% of the previous investigation up to 2003, and it is found that these size is applicable to use as bladder DDS in human body. Less