| 研究生: |
楊婕妤 Yang, Jie-Yu |
|---|---|
| 論文名稱: |
類三碳鏈離子對雙親分子形成之陰陽離子液胞的膽汁酸誘導酸鹼響應特性 Bile acid-induced pH-responsive characteristics of catanionic vesicles formed of pseudotriple-chained ion pair amphiphile |
| 指導教授: |
張鑑祥
Chang, Chien-Hsiang |
| 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: | 2024 |
| 畢業學年度: | 112 |
| 語文別: | 中文 |
| 論文頁數: | 136 |
| 中文關鍵詞: | 陰陽離子液胞 、去氧膽酸 、酸鹼響應藥物載體 、離子對雙親分子 |
| 外文關鍵詞: | Catanionic vesicle, deoxycholic acid, drug delivery carrier, ion pair amphiphile |
| 相關次數: | 點閱:45 下載:0 |
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液胞(vesicle)結構作為藥物載體具有相當大的潛力,本研究由離子對雙親分子dodecyltrimethylammonium-dihexadecyl phosphate (DTMA-DHDP)製備陰陽離子液胞,添加不同比率去氧膽酸deoxycholic acid (DCA)以誘導陰陽離子液胞的酸鹼響應特性,並探討添加去氧膽酸對液胞物理特性與雙層膜結構流動性的影響,以及對環境(pH 5.0、6.6及7.4)的應答特性。動態光散射法分析結果顯示由DTMA-DHDP製備成的液胞穩定且帶負電,添加15~45 mol%的DCA會使液胞結構不穩定,5、10、50、60 mol%則可以形成穩定的液胞。利用螢光偏極化法量測液胞雙層膜結構的排列情形,顯示添加高濃度的去氧膽酸會使雙層膜結構的排列較整齊,推測去氧膽酸上的固醇環限制了雙層膜結構中分子碳鏈的擺動。當環境pH改變至6.6時,添加50、60mol%去氧膽酸的液胞雙層膜結構的分子排列最為紊亂,可能因為此環境下解離與未解離的去氧膽酸比例約為1:1 (去氧膽酸的pKa為6.58),親疏水性相異導致位於雙層膜結構中位置不同的去氧膽酸同時存在而擾亂了分子碳鏈的排列。藥物釋放實驗可以觀察到類似的趨勢,添加50mol%去氧膽酸的液胞釋放藥物的速率高於無添加去氧膽酸的液胞。這些結果顯示添加一定量的去氧膽酸所製備的陰陽離子液胞可以響應環境pH的變化,並反映在雙層膜結構的排列上。
In the study, the effects of deoxycholic acid (DCA) on physical properties and bilayer fluidity of catanionic vesicles and the vesicle response to different environments (pH 5.0, 6.6 and 7.4) were investigated. A pseudotriple-chained ion pair amphiphile, dodecyltrimethylammonium-dihexadecyl phosphate (DTMA-DHDP), with added DCA were used to fabricate catanionic vesicles by a thin-film method. The addition of 15-45 mol% DCA would destabilize the vesicle structure. However, with 5, 10, 50 and 60 mol% DCA, stable vesicles were successfully fabricated. The fluorescence polarization (FP) analysis indicated that adding 50-60 mol% of DCA resulted in a more ordered arrangement of the vesicular bilayer structures, probably due to the sterol ring of DCA restricting the movement of hydrocarbon chains in the bilayer structures. When the environmental pH was adjusted to 6.6, the vesicles with 50 and 60 mol% DCA exhibited the disordered bilayer arrangement. At pH 6.6, the ratio of dissociated to undissociated DCA would be about 1:1 (pKa of DCA is 6.58). The dissociated and undissociated DCA with different hydrophobicity would stay at different positions in the bilayer structures and might disturb the bilayer structures. The similar trend was observed in the drug release experiments, where the vesicles with 50 mol% DCA exhibited a higher drug release rate than those without DCA. The results suggested that the catanionic vesicles fabricated with a specific amount of DCA could response to environmental pH, leading to a change in the bilayer structure arrangement.
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校內:2029-08-22公開