研究生: |
張峻瑋 |
---|---|
論文名稱: |
多功能之酸鹼應答型高分子複合液胞於藥物傳遞與核磁共振應用之探討 Multifunctional pH-responsive polymer hybrid vesicles for drug delivery and magnetic resonance study |
指導教授: | 邱信程 |
口試委員: |
林松池
謝文元 邱信程 |
學位類別: |
碩士 Master |
系所名稱: |
原子科學院 - 生醫工程與環境科學系 Department of Biomedical Engineering and Environmental Sciences |
論文出版年: | 2011 |
畢業學年度: | 99 |
語文別: | 中文 |
論文頁數: | 59 |
中文關鍵詞: | 核磁共振 、藥物控制釋放 |
相關次數: | 點閱:2 下載:0 |
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本研究中製備出具多功能的酸鹼應答型複合式液胞,此液胞功能包括兼具抗癌藥物的控制釋放與高靈敏性核磁共振顯影功能。本研究利用離子化的聚丙烯酸(poly(acrylic acid))和釓離子螯合,接著再藉由添加少量的(佔AAc的5mol% )陽離子型脂質1,2-Dioleoyl-3-Trimethylammonium-Propane (DOTAP)與帶負電的聚丙烯酸(已吸附釓離子)吸附,形成液胞結構。隨後再利用靜電作用力將抗癌藥物doxorubicin (DOX)吸附於液胞內。此時將液胞溶液添加 EDC/NHS及2,2-(Ethylenedioxy)bis(ethylamide)進行交聯。此交聯後的液胞可抵抗高濃度鹽類的破壞,並且穩定性佳。為了設計出對所處環境pH具應答性的核磁共振造影劑,生物相容性高分子幾丁聚醣(chitosan)和γ-PGA(OSu)-g-PEG以layer-by-layer的方式逐步吸附到高分子複合液胞表面。此外,由於γ-PGA(OSu)-g-PEG高分子帶有具反應性的官能基-OSu,可更進一步與chitosan上的胺基進行交聯,提高液胞於溶液內的穩定性。此液胞複合可利用chitosan具酸鹼應答的特性,控制水分子對液胞膜的通透程度,進而調控溶液的縱向鬆弛速率。另外,於藥物控制釋放的測試中,可發現於pH 4.7環境下,藥物可於短時間內(10小時)累積釋放70 %,於pH 7.4環境下,則僅有約25 %的累積釋放。顯示此液胞可利用pH-trigger的特性而達到藥物釋放的目的。於細胞毒性測試的研究中,則發現未吸附DOX的高分子複合液胞不具有明顯細胞毒性。包覆DOX的藥物載體其毒殺癌細胞的效率略低於僅添加抗癌藥物的控制組。因此,此具有酸鹼應答的多功能複合液胞於癌症治療及臨床診斷的領域內是具有極高的潛力的。
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