以脂質與大量乙醇為主材料所形成的乙醇體(ethosome)液胞系統經研究證實可促進藥物在皮膚上的傳輸能力。本研究先以陽離子型界面活性劑(decyltrimethylammonium bromide, DeTMAB)和陰離子型界面活性劑(sodium dodecyl sulfate, SDS)等莫耳混合合成DeTMA-DS離子對雙親分子(ion pair amphiphile, IPA)，並以此IPA為主材料在半自發製程下添加合適量的乙醇與膽固醇形成類乙醇體陰陽離子液胞(ethosome-like catanionic vesicle)，並與脂質(PL-90)和乙醇所形成的乙醇體作比較，期待能作為經皮藥物傳輸用之載體。乙醇與膽固醇影響液胞的物理特性以粒徑、界面電位、存活期、雙層膜固化性進行有系統地分析；並利用油溶性維他命E醋酸酯(α-tocopherol acetate, α-TA)和水溶性羧基螢光素(5(6)-carboxyfluorescein, CF)作為模擬藥物評估液胞的包覆/釋放能力。此外，液胞藉由添加有/無疏水修飾的水溶性聚陽離子電解質(HMP+和P+)探討其膠化行為。
結果顯示在一合適的乙醇濃度範圍下可生成足夠穩定的乙醇體與類乙醇體陰陽離子液胞。此外，膽固醇適量的添加可進一步提升類乙醇體陰陽離子液胞的存活期，但是不利於乙醇體的生成。另一方面，液胞雙層膜固化性(疏水性)會受到乙醇的添加些微降低，而受到膽固醇的添加明顯上升。
在乙醇體與類乙醇體陰陽離子液胞包覆α-TA的結果上，乙醇影響藥物分布在液胞油/水區域量的不同導致包覆效率與乙醇濃度呈現一負相關趨勢。對於類乙醇體陰陽離子液胞包覆與釋放CF的結果上，乙醇濃度的增加使包覆效率與釋放半衰期分別呈現些微與明顯的下降。這些結果與乙醇影響藥物在液胞油/水區域分布量和雙層膜固化性有關。此外，含較高膽固醇量的類乙醇體陰陽離子液胞可包覆較多的α-TA與CF，並且有較長的CF釋放半衰期，顯示與雙層膜具有較高的固化性有關。
膠化的結果發現類乙醇體陰陽離子液胞與HMP+的交互作用受到乙醇濃度與膽固醇含量的增加，分別呈現減弱與增強的趨勢。對液胞與P+的交互作用而言，則不受乙醇與膽固醇的影響。這些發現說明了液胞與高分子間的交互作用主要為疏水而不是靜電作用力主導。此外，類似的結果也在乙醇效應影響乙醇體與HMP+或P+的膠化中顯示。
相較於乙醇體藉由乙醇調控物理穩定性、包覆/釋放與膠化行為，類乙醇體陰陽離子液胞能同時藉由乙醇與膽固醇的調控改變液胞的物理穩定性、包覆/釋放與膠化行為，因此具有更大的操作彈性於未來經皮藥物傳輸上。

A carrier for enhanced skin delivery of drugs has ever been discovered and named ‘‘ethosomes,’’ which are phospholipid vesicular systems embodying ethanol in relatively high concentrations. In this work, we synthesized the decyltrimethylammonium-dodecylsulfate (DeTMA-DS) ion pair amphiphile (IPA) by equal molar mixing of decyltrimethylammonium bromide (DeTMAB) and sodium dodecyl sulfate solutions (SDS). Ethosome-like catanionic vesicles, which are compose of DeTMA-DS IPA, ethanol, and cholesterol, were then prepared through a semispontaneous process for possible dermal drug delivery. Ethosomes, which are composed of PL-90 lipid and ethanol, were also prepared to be a counterpart of ethosome-like catanionic vesicles. The effects of ethanol and cholesterol on the physical characteristics such as size, zeta potential, lifetime, and bilayer membrane rigidity of ethosomes and ethosome-like catanionic vesicles were systematically studied. The encapsulation/release behavior of vesicles by encapsulating hydrophobic α-tocopherol acetate (α-TA) and hydrophilic 5(6)-carboxyfluorescein (CF) and gelation of vesicles by water-souble polycations with and without hydrophobic modification (HMP+ and P+) were therefore discussed.
The experimental results revealed that ethosomes and ethosome-like catanionic vesicles with an optimized amount of ethanol could result in a reasonable lifetime. Furthermore, although inclusion of cholesterol in bilayers could not form stable ethosomes, it further enhanced lifetime of the ethosome-like catanionic vesicles. On the other hand, while the vesicular membrane rigidity (hydrophobicity) was slightly deteriorated by ethanol, it was greatly enhanced by cholesterol.
For the α-TA encapsulation of ethosomes and ethosome-like catanionic vesicles, the results indicated that the ethanol effect on the partition of the α-TA between vesicular bilayer and core regions led to negative relations between ethanol concentration and encapsulation efficiency. As for the CF encapsulation and release of ethosome-like catanionic vesicles, the encapsulation efficiency and half-release time, respectively, slightly and significantly decrease with the increasing ethanol concentration. These findings are due to the effects of ethanol on the partition of the CF between vesicular bilayer and core regions and vesicular membrane hydrophobicity. On the other hand, more rigid and hydrophobic catanionic vesicular membranes caused by the addition of cholesterol would encapsulate more α-TA and CF drugs and further prolong the half-release time of CF.
For the gelation results of the ethosome-like catanionic vesicle/polymer mixtures, the interaction between vesicle and polymer HMP+ decreases and increases with the increasing ethanol concentration and cholesterol content, respectively. Both ethanol concentration and cholesterol content, however, showed little effects on the interaction between vesicle and polymer P+. These findings lead to the conclusion that the gelation of ethosome-like catanionic vesicles by polymer molecules is driven by the hydrophobic more than the electrostatic interactions. In addition, similar conclusion was also found for the ethanol effects on the gelation of ethosomes by HMP+ and P+.
The lifetime, vesicular membrane rigidity, encapsulation/release, and gelation of ethosome-like catanionic vesicles can be well tailored by ethanol and cholesterol in comparison with those of ethosomes, in which were only tailored by ethanol. This fact may have a potential in developing new formulations for dermal drug delivery.

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