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Title: | 超音波結合微氣泡強化奈米顆粒與大分子在腦組織之累積與磁振造影之監控 Enhancement of Nanoparticle and Macromolecule Delivery into Brain Tissue with Ultrasound and Microbubbles and Monitoring with MR Image |
Authors: | Hsin-Yu Wu 吳欣瑜 |
Advisor: | 林文澧 |
Keyword: | 聚焦式超音波,超音波顯影劑,血腦屏障,藥物輸送,奈米粒子, focused ultrasound,microbubbles,blood-brain barrier,drug delivery,nanoparticles, |
Publication Year : | 2010 |
Degree: | 碩士 |
Abstract: | 在腦部疾病治療中,血腦屏障是欲傳遞藥物的主要限制,而聚焦式超音波可以非侵入性並且選擇性的使血腦屏障暫時通透,使得原本無法通過的大分子進入腦中。但若傳遞效率太低仍不足以治療腦部疾病。本研究探討以1 MHz的聚焦式超音波搭配超音波顯影劑將血腦屏障開啟後,在相同位置再施予一次聚焦式超音波不再注射超音波顯影劑來強化藥物輸送的效果。同時也比較不同大小的粒子在相同超音波參數下開啟血腦屏障傳遞的情形,以及多施打一次超音波對不同大小粒子所造成的影響。
本實驗使用300- 400克大鼠,僅剃除頭頂毛髮後進行超音波治療。超音波參數為1 Hz重複頻率、10 ms脈衝長度、震盪時間60秒,以水診器量測經頭殼衰減後之聲壓為0.54 MPa。將血腦屏障暫時開啟後,注射欲傳遞到腦中的粒子(本實驗使用70 nm氧化鐵、3 kDa和70 kDa dextran),待超音波顯影劑衰減後在相同位置施打第二次超音波。實驗完成後以感應耦合電漿質譜儀和微盤分光光譜儀定量腦中粒子含量。 由感應耦合電漿質譜儀定量出強化組和非強化組的腦中的鐵離子含量有統計學上顯著差異,氧化鐵同時也是磁振造影T2*WI顯影劑,可以在即時影像上監控氧化鐵進入腦中含量。微盤分光光譜儀結果指出,在血腦屏障開啟情況下,3 kDa dextran進入腦中的量較70 kDa dextran多,但多給予一次超音波震盪,70 kDa dextran進入腦中的量大幅提升,和原本相比具有統計學上顯著差異;而3 kDa dextran的強化組與非強化組則差異不大。此結果可顯示,經由上述治療策略來強化粒子在腦組織輸送,在較大的粒子上其強化效果較顯著。 The blood-brain barrier (BBB) is the major limiting factor to delivering therapeutic agents to the brain for disease treatment. Focused ultrasound (FUS) was shown to be able to noninvasively and selectively deliver compounds at pharmacologically relevant molecular weights through the opened BBB. In this study, we investigated the delivery enhancement of nanoparticles and macromolecules into brain tissue using additional sonication after the BBB was temporarily opened by FUS with microbubbles. We examined the BBB opening induced by FUS and microbubbles dependence on the agent’s molecular weight with MR image and inductively coupled plasma mass spectrometry (ICP-MS). After the injection of microbubbles, one MHz FUS immediately sonicated at the target location of the brains of 300-400g Wistar rats through skulls to noninvasively open the BBB. After the complete decay of microbubbles, an additional sonication was applied without further microbubble injection to enhance the delivery of iron oxide (70 nm) or dextran (3 kDa or 70 kDa) particles into the sonicated brain tissues. The amount of particles in the brain tissue was measured using ICP-MS and microplate reader. ICP-MS results showed that FUS with a low dosage of microbubbles could only result in a small amount of iron oxide nanoparticles delivered into the brain tissues (extracellular space~50nm). However, an additional FUS sonication could enhance nanoparticles delivered into brain tissues up to 20-fold. The result of microplate reader showed that 3 kDa and 70 kDa dextrans were both diffusively distributed throughout the targeted brain region, while 70 kDa dextran appeared more punctuative. The amount of 70 kDa dextran significantly increased with an additional sonication, but not for 3 kDa dextran. This sonication strategy can effectively enhance the delivery of nanoparticles and macromolecules into the sonicated brain tissues, and it is more effectively to larger macromolecules and to nanoparticle with low dose of microbubble injection. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/45803 |
Fulltext Rights: | 有償授權 |
Appears in Collections: | 醫學工程學研究所 |
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ntu-99-1.pdf Restricted Access | 1.11 MB | Adobe PDF |
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