陰陽離子界面活性劑(catanionic surfactant)又稱為離子對雙親分子(ion-pair amphiphile, IPA) 。其分子結構類似脂質，同時具有價格低廉、化學穩定性，化學結構可設計等優點，為一製備液胞藥物載體的新型材料。本研究透過沉澱法合成陰陽離子界面活性劑DeTMA-TS (decyltrimethylammonium-tetradecylsulfate, C10-C14)，並添加不同比例的膽固醇(XCHOL= 0～0.5)作為膜內穩定劑，透過強制製程製備陰陽離子液胞分散液，探討膽固醇濃度及製程溫度對其物理特性之影響。並利用螢光偏極化方法測定液胞雙層膜堅硬度，進一步探討液胞粒徑和雙層膜堅硬度之間的關聯，以驗證強制製程液胞形成之機制。為探討液胞的藥物包覆行為，另以緩衝溶液(Tris-HCL buffer, pH= 7.4)製備液胞分散液以模擬人體生理環境，並包覆親水性藥物熊果素(Arbutin)，分析其物理特性和包覆效率之關聯。
實驗結果顯示添加膽固醇有助於提升液胞的物理穩定性。隨著膽固醇濃度增加，液胞粒徑增大，螢光非等向性(anisotropy) r值也提升，顯示雙層膜堅硬度也會增加。此外，製程溫度也會影響液胞的粒徑和雙層膜堅硬度。在高於雙層膜相轉移溫度(Tm)的條件下，製程溫度愈低，雙層膜愈堅硬，液胞粒徑也較大。分析實驗結果顯示液胞粒徑和雙層膜堅硬度之間具有高度的線性正相關，這也為強制製程液胞形成機制中，主張雙層膜堅硬度愈大，形成的液胞粒徑也愈大，提供了有力的證據。此一結論也可在其他種類的陰陽離子液胞及脂質體的製備獲得驗證。此外，親水性藥物熊果素的包覆實驗結果顯示，隨著膽固醇濃度增加，粒徑隨之增大，而包覆效率也跟著提升，液胞粒徑和包覆效率呈現正相關。本研究的最後結論是：添加劑膽固醇除了可以穩定液胞，增進雙層膜堅硬度，也可以提升液胞的粒徑，增加液胞內水相的總體積，進而提升對親水性藥物的包覆效率。

Catanionic surfactants (also known as ion-pair amphiphiles, IPAs) have emerged as attractive materials for preparing novel vesicular carriers of drug delivery systems due to their benefits of abundant sources, low cost, chemical stability, and designable chemical structure, and so on. In this work, catanionic surfactant DeTMA-TS (decyltrimethylammonium-tetradecylsulfate) was synthesized and used for the preparations of catanionic vesicles with molar fraction of cholesterol (CHOL), XCHOL, ranging from 0 to 0.5 by a mechanical disruption approach. Effects of CHOL and process temperature on the physical properties of catanionic vesicles were investigated. Furthermore, fluorescence polarization technique was employed to measure the ordering and rigidity of vesicular bilayers. Relationship between the steady state fluorescence anisotropy (r) and vesicle diameter (D) was established with the aim to validate the mechanism of vesicle formation, which advocates that the higher the bilayer rigidity the larger the vesicle size. In addition, encapsulation efficiency of the hydrophilic drug Arbutin was also determined for the catanionic vesicles in a buffer solution.
The experimental results revealed that the physical stability of catanionic vesicles is enhanced by the addition of CHOL. Both D and r, that is bilayer rigidity, are increased with the increasing of CHOL concentration. Temperature, under which vesicles were prepared by the mechanical dispersion process, was found to be another factor that affects D and r. Lower process temperature and therefore higher r resulted in larger D. A significant positive correlation between D and r was shown by analyzing the available data. This result provided strong evidence for the mechanism of vesicle formation delineated above. Moreover, it was shown that this is also valid for vesicles prepared from other catanionic surfactants and lipid. Finally, the results of arbutin encapsulation showed that increasing CHOL concentration lead to the larger vesicle size and higher encapsulation efficiency (E.E.). There is a positive correlation between vesicle D and E.E. In conclusions, the addition of CHOL contributed to enhancing physical stability, promoting bilayer rigidity, increasing size, and improving hydrophilic drug encapsulation of catanionic vesicles.

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