本研究以類三碳鏈離子對雙親分子dihexadecyldimethylammonium-dodecylsulfate（DHDA-DS）為主材料，添加不同比率的膽固醇製備出帶正電的陰陽離子液胞，探討添加的膽固醇對所形成之陰陽離子液胞物理特性及雙層膜結構流動性的影響。此外，藉由改變液胞分散液的酸鹼度及溫度，分析液胞的環境應答特性。酸鹼應答實驗是將液胞分散液分別調整至pH 4.0、5.0、6.0、7.4及8.0，分析液胞的物理特性及雙層膜結構中分子的排列特性。溫度應答實驗是藉由升高液胞分散液的溫度，探討液胞雙層膜結構之相轉移溫度及分子排列的變化。最後以溶血實驗、細胞存活度實驗評估液胞應用的可行性。
實驗結果顯示DHDA-DS/膽固醇混合系統可形成帶正電的液胞，當膽固醇含量達40 mol%後，能大幅提升液胞的物理穩定性。藉由傅立葉轉換紅外光譜法分析液胞中整體分子碳鏈的自由度，顯示含少量膽固醇之系統中的分子碳鏈自由度較小，推測膽固醇的疏水性固醇環結構限制了鄰近碳鏈的自由度，即膽固醇在雙層膜結構中的作用以凝縮效應為主。隨著膽固醇含量持續增加，可能因膽固醇的存在造成液胞組成分子間不可忽略的空隙，使得整體的分子碳鏈自由度增加，此為膽固醇之失序效應。以上結果可反映至不同膽固醇含量之液胞雙層膜結構的相轉移溫度。
溫度應答分析顯示，每一組成下之液胞的粒徑分布不隨溫度而有明顯變化。利用動態光散射法、螢光偏極化法及傅立葉紅外光譜法評估相轉移溫度，發現含有10、20 mol％膽固醇的液胞系統有較高的相轉移溫度。由於少量膽固醇的添加對雙層膜結構的影響以凝縮效應為主，相轉移溫度因而較高。高膽固醇含量對雙層膜結構具失序效應，分子的碳鏈自由度較高，相轉移溫度因而較低。
由DHDA-DS/膽固醇混合系統製備出的液胞分散液pH值約為6.0，接近所使用純水的pH值。當分散液的pH值調整至4.0或5.0時，液胞的界面電位微幅上升，但粒徑分布幾乎沒有改變。由於液胞間有較強的靜電排斥作用能避免聚集，使pH 4.0～6.0範圍下的粒徑分布不隨pH值而改變。當環境pH值為7.4時，液胞的界面電位明顯下降，出現少量較大粒徑的聚集體，液胞的穩定性少於三天，推測是液胞間微弱的排斥作用造成聚集。當液胞分散液的pH值調整至8.0時，液胞立即不穩定。以上特性顯示此液胞系統適用於鹼性環境的藥物釋放應用。此外，利用螢光偏極化法及傅立葉紅外光譜法分析不同酸鹼環境下液胞中分子的排列情形，發現液胞雙層膜結構中分子的碳鏈自由度幾乎不受環境酸鹼度影響。
為了評估液胞應用的可行性，以人類非小肺癌細胞株及正常人類上皮細胞進行細胞存活率檢測，並以溶血實驗分析液胞對紅血球的影響，結果顯示低濃度的液胞分散液具可接受的細胞毒性及溶血率。此外，高膽固醇含量之液胞不僅有穩定性佳的特性，生物毒性也較低。

In this study, pseudo triple-chained ion pair amphiphile, dihexadecyldimethylammonium-dodecylsulfate (DHDA-DS), was used as the main material to fabricate positively charged catanionic vesicles with the addition of various contents of cholesterol. The effects of added cholesterol on physical properties and bilayer structure fluidity of the catanionic vesicles were then investigated. Besides, environment-responsive characteristics of the vesicles were analyzed by changing the pH and temperature of the vesicle dispersions. pH-responsive experiments were performed by adjusting the vesicle dispersions to 4.0, 5.0, 6.0, 7.4, and 8.0, respectively, and physical properties of the vesicles and molecular packing characteristics of the bilayer structures were analyzed. Thermo-responsive experiments were carried out by increasing temperature of the vesicle dispersions to evaluate the phase transition temperature and molecular packing change of the vesicular bilayer structures. Hemolysis experiments and cytotoxicity tests were adopted to evaluate feasibility of the vesicle application.
The experimental results indicated that positively charged catanionic vesicles could be fabricated from the mixed DHDA-DS/cholesterol system. When the cholesterol content was higher than 40 mol%, physical stability of the vesicles could be significantly enhanced. The motion freedom of whole molecular hydrocarbon chains in the vesicles was analyzed by FTIR, and less motion freedom of the molecular hydrocarbon chains was found for the systems with low cholesterol contents. This is probably because the hydrophobic and rigid sterol ring of cholesterol restrained the motion freedom of neighboring hydrocarbon chains, and the influence of cholesterol on the bilayer structures was dominated by the condensing effect. As cholesterol content was increased, the space between the vesicle-forming molecules probably induced by cholesterol could not be ignored, resulting in increased motion freedom of the whole molecular hydrocarbon chains. This is the disordering effect of cholesterol. The above results were reflected in the phase transition temperature of the vesicular bilayer structures with different cholesterol contents.
Thermo-responsive analysis indicated that the size distributions of the vesicles containing various cholesterol contents were not significantly affected by temperature changes. By using DLS, FP, and FTIR methods, one was able to evaluate the phase transition temperatures and higher phase transition temperatures were found for the vesicles containing 10 or 20 mol% cholesterol. The influence of cholesterol with low contents on bilayer structures was dominated by the condensing effect, resulting in the higher phase transition temperatures. The influence of cholesterol with high contents on bilayer structures was dominated by the disordering effect, and thus the motion freedom of molecular hydrocarbon chains became high, leading to lower phase transition temperatures.
The pH of the vesicle dispersions fabricated from DHDA-DS/cholesterol mixtures was about 6.0, which was close to pH of pure water. When the pH of the vesicle dispersions was adjusted to 4.0 or 5.0, zeta potential of the vesicles was slightly increased, but the vesicule size distributions were almost the same. Since stronger electrostatic repulsion between the vesicles could prevent aggregation, the vesicle size distributions in the pH range of 4.0～6.0 were not changed with pH variation. As the pH was adjusted to 7.4, zeta potential of the vesicles was significantly decreased, and some large aggregates appeared with the vesicle stability less than 3 days. The aggregation was probably caused by weak repulsion between the vesicles.
When the pH of the vesicle dispersions was adjusted to 8.0, vesicles immediately became unstable. The above results suggested that this vesicle system was suitable for the drug release application in alkaline environment. In addition, the molecular packing in the vesicles at different pH conditions was investigated by FP and FTIR analyses. It was found that the motion freedom of molecular hydrocarbon chains in the vesicular bilayer structures was hardly affected by pH of the environment.
In order to evaluate the application feasibility of the vesicles, cell viability was examined with human non-small lung carcinoma cell line and human bronchial epithelial cells, and the effect of the vesicles on red blood cells was analyzed by hemolysis experiment. The results showed that the cytotoxicity and hemolysis ratio were acceptable for the vesicle dispersions with low concentrations. In addition, the vesicles with high cholesterol contents possessed not only high stability but also low cytotoxicity.

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