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研究生: 蘇資淵
Su, Tzu-Yuan
論文名稱: PLGA多孔微粒披覆微脂體雙組成之多功能藥物傳遞系統
Extracellular and Intracellular Drug Delivery Systems Composed of Porous PLGA Microspheres Covered with Liposomes
指導教授: 宋信文
口試委員: 邱信程
宋信文
許明照
陳三元
王麗芳
學位類別: 碩士
Master
系所名稱: 工學院 - 化學工程學系
Department of Chemical Engineering
論文出版年: 2012
畢業學年度: 100
語文別: 中文
論文頁數: 43
中文關鍵詞: PLGA多孔微粒雙乳化微脂體Doxorubicin藥物傳輸
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  •   臨床上,癌症治療除了以抗癌藥物直接造成癌組織的死亡之外,常同時搭配血管新生抑制劑,阻斷患部的血管新生,避免殘餘的癌組織持續獲取營養繼續成長以及可能發生的轉移。傳統上,PLGA藥物載體大多應用於長效釋放,其釋放機制主要為PLGA微粒水解後的藥物釋放,其於癌症的治療上,常被質疑可能造成患部藥物濃度不足的疑慮。本研究以治療癌症為模擬應用目標,利用雙乳化方法製備出表面具有奈米級孔洞的PLGA微球,其上披覆能與細胞快速融合的微脂體,提出一可兩階段控制釋放系統: 微脂體進行細胞融合快速於胞內釋放第一階段抗癌藥物,PLGA多孔微球則於其後進行第二階段胞外釋放藥物。
      實驗分為三大部分,第一部分為利用雙乳化方法製備出PLGA多孔微粒,探討不同濃度PBS對於PLGA微粒表面孔洞形態的影響,找出最適化的參數。第二部分則是檢驗不同孔洞大小的PLGA微粒以及表面披覆有微脂體的微粒,放置於模擬體內環境的PBS緩衝液下,探討包覆於PLGA多孔微粒其中的Hoechst釋放情形;同時也利用掃描式電子顯微鏡觀察披覆微脂體後微粒表面形態的改變。第三部份是以人類纖維肉瘤細胞(HT1080)做為細胞測試的模型,將披覆微脂體的PLGA微粒與細胞共培養後,利用螢光顯微鏡觀察細胞膜與細胞核是否會分別呈現出綠色螢光及紅色螢光以驗證微脂體與細胞膜融合並且釋放藥物Doxorubicin,並觀察帶有螢光染劑(DiD)的PLGA多孔微粒是否可避免被細胞吞食停留在細胞外釋放第二種藥物。由以上三部分的實驗可驗證我們所製備的微脂體能夠迅速與細胞膜融合於胞內釋放第一種藥物,而PLGA多孔微粒則可以避免被細胞吞噬在胞外釋放第二種藥物。藉由此二階段藥物釋放劑型,可使抗癌藥物Doxorubicin迅速於胞內釋放毒殺癌細胞,再於胞外緩慢釋放作用期較長之抑制血管新生藥物,加強前者的療效,而改善、提高癌症之治療效果。


    摘要.....I 圖目錄.....IV 表目錄.....VI 第一章 緒論.....1 1-1 藥物制放系統.....1 1-2 生物可降解性高分子材料.....2 1-3 乳化系統的製備方法.....3 1-4 多孔性高分子基材.....5 1-5 小紅莓 (Doxorubicin).....6 1-6 微脂體 (Liposome).....7 1-6.1 微脂體簡介.....7 1-6.2 微脂體結構.....8 1.6-3 微脂體之粒形.....8 1-7 抑制血管新生療法.....10 1-7.1 血管新生.....10 1-7.2 抗血管新生療法.....11 1-7.3 未來發展方向.....11 1-8 研究動機與目的.....13 第二章 製程與實驗.....17 2-1 利用雙乳化方法製備不同大小孔洞的PLGA微粒.....17 2-2 以薄膜水合法製備微脂體.....19 2-3 不同孔洞大小PLGA微粒及披覆微脂體之PLGA微粒體外釋放(in vitro).....20 2-4利用HT1080細胞株探討披覆微脂體之PLGA微粒二階段釋放能力(in vitro).....22 第三章 結果與討論.....25 3-1 PLGA微粒製作之Morphology.....25 3-2 微脂體製作之Morphology.....27 3-3 PLGA多孔微粒釋放結果.....28 3-3.1 不同孔洞大小微粒之釋放曲線圖.....28 3.3-2 披覆微脂體之PLGA微粒釋放曲線圖.....30 3-4利用HT1080細胞株探討披覆微脂體之PLGA微粒二階段釋放能力(in vitro).....33 第四章 結論.....40 參考文獻.....41

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