| 研究生: |
林侑聖 Lin, Yu-Sheng |
|---|---|
| 論文名稱: |
維生素E醋酸酯誘導膽固醇雙層結構域形成對類乙醇體陰陽離子液胞雙層膜堅硬度的影響 Effects of Vitamin E Acetate-Induced CBD Formation on the Bilayer Rigidity of Ethosome-Like Catanionic Vesicles |
| 指導教授: |
楊毓民
Yang, Yu-Min |
| 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: | 2023 |
| 畢業學年度: | 111 |
| 語文別: | 中文 |
| 論文頁數: | 83 |
| 中文關鍵詞: | 類乙醇體陰陽離子液胞 、乙醇 、膽固醇 、維生素E醋酸酯 、雙層膜堅硬度 、膽固醇雙層結構域 、螢光非等向性技術 、經皮藥物傳輸系統 |
| 外文關鍵詞: | Ethosome-like catanionic vesicle, Vitamin E acetate, Bilayer rigidity, Cholesterol bilayer domain, Transdermal drug delivery |
| 相關次數: | 點閱:101 下載:7 |
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類乙醇體陰陽離子液胞已成為潛在的藥物載體。本研究利用沉澱法得到結構類似於脂質的離子對雙親分子DeTMA-TS (decyltrimethylammonium-tetradecylsulfate, C10-C14)作為主材料經由半自發的製程製備液胞,改變不同乙醇濃度(10 vol%-30 vol%)和添加不同比例的膽固醇(XCHOL=0.2-0.7),包覆不同濃度的維生素E醋酸酯(油溶性藥物),及pH值為7.4的緩衝溶液(Tris-HCL buffer)得到類乙醇體陰陽離子液胞分散液。利用螢光非等向性(FP)技術來測定螢光非等向性值(r),其代表液胞雙層膜的堅硬度,藉由雙層膜堅硬度來探討雙層膜中膽固醇和維生素E醋酸酯的交互作用。
首先討論在乙醇濃度20 vol%及溫度35 °C下,在沒有包覆維生素E醋酸酯時,在膽固醇莫爾分率0.6以下,膜堅硬度隨著膽固醇添加呈線性增加,這是膽固醇的凝縮效應,當超過0.6時,膜堅硬度隨著膽固醇增加而下降由於形成膽固醇雙層結構域(CBD)。當有包覆維生素E醋酸酯時,在低濃度膽固醇下,由於其藥物結構性質會垂直並錨定在雙層的兩側使得膜堅硬度上升,r值最大能增加9%,然而,當膽固醇超過一定濃度,一定量的維生素E醋酸酯會誘導部分膽固醇形成膽固醇雙層結構域,削弱了原先的膽固醇效應使得膜堅硬度開始下降,r值最大能降低13%。隨著膽固醇濃度愈高,愈少量的維生素E醋酸酯即可形成膽固醇雙層結構域。這也使得原先膽固醇雙層結構域需要在膽固醇莫爾分率0.6下形成,有了維生素E醋酸酯包覆,可以降低至膽固醇莫爾分率0.25。隨後也發現膽固醇雙層結構域所形成的濃度範圍,會隨著乙醇濃度愈高,範圍變廣,在10 vol%乙醇下,膽固醇莫爾分率需0.3才可形成膽固醇雙層結構域,但在30 vol%乙醇下,在膽固醇莫爾分率0.2時,就可形成膽固醇雙層結構域。兩者交互作用的機制可適用實驗溫度範圍為25 °C到40 °C。
同時也透過檢測其液胞穩定性與膜堅硬度來找出最適合做為經皮藥物傳輸載體的配方,在穩定性上,其穩定天數高達200天以上,而包覆維生素E醋酸酯的類乙醇體陰陽離子液胞其雙層膜堅硬度相對於乙醇體(DPPC, dipalmitoylphosphatidylcholine)小,因此指出其具有足夠軟的液胞雙層膜結構,可用於經皮傳輸系統。
Lipid-like ion-pair amphiphile vesicles have emerged as potential drug carriers. This study employed a semi-spontaneous process to prepare vesicles and encapsulated vitamin E acetate (VEA, an oil-soluble drug).The anisotropy (r) was measured using fluorescence polarization (FP) method to investigate the interaction between cholesterol (CHOL) and VEA within the bilayer. At an ethanol concentration of 20 vol% and a temperature of 35°C, it can be observed that in the absence of VEA encapsulation, the r increased due to the condensing effect. However, when CHOL concentration exceeded XCHOL is 0.6, cholesterol bilayer domain (CBD) formed, leading to decreased r. At low CHOL concentrations, higher VEA concentrations increased r, up to a maximum of 9%. Its structural properties contributed to its anchoring in the bilayer. As the CHOL concentration increases, VEA induces the formation of CBD, resulting in a decrease in the r value with a maximum decrease of 13%. With higher CHOL concentration, a lower amount of VEA is required to form CBD. This also led to a reduction in the CBD from XCHOL is 0.6 to 0.25. Subsequently, it was found that with increasing ethanol concentration, the concentration range for CBD formation expands. Under 10 vol% ethanol, CBD formed at XCHOL is 0.3, while under 30 vol% ethanol, CBD formed at XCHOL is 0.2. This interaction was applicable within a temperature range of 25°C to 40°C. The vesicles encapsulated VEA exhibited a lifetime over 200 days, with softer bilayer compared to ethosomes (dipalmitoylphosphatidylcholine, DPPC), making it suitable for transdermal delivery systems.
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