本論文主要在探討微米級的藥物膠體粒子透過血液傳遞時，經由主動脈血管壁的內皮細胞間縫滲漏到腫瘤組織中，並且導入腫瘤細胞的深層組織時，以網絡模型模擬藥物粒子在腫瘤細胞內的吸附與釋放行為。其中，將腫瘤細胞內變異細胞間的空隙視為單一楔型管的形狀，再由多個楔型管所組成的圓環狀網絡系統，以不同的主動脈血液流速、主動脈壓力、腫瘤內部壓力及微血管管徑，對藥物粒子的吸附行為進行模擬，比較其結果並探討。 模擬結果發現，在相同的主動脈血管壓力、腫瘤內部壓力差下，主動脈血液流速是影響藥物粒子是否可以擴散至腫瘤內部的主要原因，而主動脈血液流速，會直接影響進入腫瘤區域的藥物粒子濃度分佈。較大的主動脈血液流速伴隨著大量的藥物粒子進入，會造成藥物粒子集中於腫瘤前端吸附。而較小的主動脈血液流速反而可以使藥物粒子擴散至腫瘤內部進行吸附。在相同的腫瘤內部壓力差和主動脈血液流速下，主動脈血管壓力較小時，同一層被吸附的藥物粒子數量較多，而當主動脈血管壓力增加時同一層被吸附的藥物粒子數量則較少，這是因為主動脈血管壓力Pc=20mmHg時，微血管當中的血液流速比主動脈血管壓力Pc=10mmHg時還小，單位時間內進入腫瘤區域的藥物粒子相對減少，雖然此時會造成吸附範圍增加，但是腫瘤區域每一層可吸附的藥物粒子數卻有減少的趨勢，此情形在增加主動脈血管流速時會更明顯。在相同的主動脈壓力、腫瘤內部壓力差下，在較大的微血管半徑中，藥物粒子所能吸附的量較為平均。因為微血管管徑的增加，使藥物粒子不會集中於腫瘤的前端進行吸附，有助於藥物粒子深入腫瘤內部，在此情形下，改變主動脈血液流速對於藥物粒子擴散至腫瘤內部進行吸附的影響較不顯著。 By treating the drugs as the colloidal particles, the main purpose of this thesis is to simulate the drug delivery phenomena in a tumor cell by using the modified square network model when drugs pass through the tube wall of an artery into the microvascular tumor cells. In the present thesis, the sinusoidal constricted tube model which composes of the network was adopted to simulate the tumor microvascular structure. The effects of aortic blood velocity, the aortic pressure, the internal pressure of the tumor and the radius of tumor cell on the breakthrough concentration of drugs are investigated theoretically in the present thesis.The simulation results show that: (1) Under the same values of the drug dosage and the difference between the aortic pressure and the internal pressure of the tumor, a steep drug concentration gradient distribution will be induced at the entrance of the artery when the aortic blood velocity is high, which will make those drugs accumulate at the entrance zone of the tumor cells at the initial delivery period, but a low artery blood velocity can drive those drugs to deliver at the inside zone of the cells. (2) Under the same values of the aortic blood velocity, the aortic pressure and the drug dosage, those drugs will deliver to the same layer, no matter what size of the tumor cells is. When the tumor cell becomes larger, more drugs can be adsorbed in each layer of the tumor. (3) Under the same values of the aortic blood velocity and the same internal pressure of the tumor, when the microvascular radius of the tumor cell becomes larger, more drugs will be delivered to the inside zone of the cells at the later delivery period.
