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研究生: 潘諾娜
Pandiangan, Florentina
論文名稱: 由14碳/12碳陰陽離子界面活性劑和膽固醇製備之液胞結構的物理性質及穩定性
Physical properties and stability of vesicular structures fabricated from C14/C12 catanionic surfactant with cholesterol
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: 2020
畢業學年度: 108
語文別: 英文
論文頁數: 79
外文關鍵詞: Catanionic vesicle, encapsulation efficiency, mixed cationic/anionic surfactants, vesicular structure
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  • Vesicular structures of catanionic surfactants fabricated from mixed cationic and anionic surfactants in aqueous phase can be applied as drug delivery carriers. In this study, stable catanionic vesicles were fabricated from mixed cationic/anionic surfactants with different molar ratios, and then various concentrations of vitamin E acetate (VEA) as hydrophobic model drug and 30 mM arbutin as hydrophilic model drug were encapsulated. In addition, in vitro release behaviour of the encapsulated arbutin from the catanionic vesicles was investigated. Tetradecyltrimethylammonium bromide (TTMAB), a cationic surfactant, and sodium dodecylsulfate (SDS), an anionic surfactant, were used as the raw materials for the formation of the catanionic vesicles. A semi-spontaneous formation process was adopted to form the catanionic vesicles in ethanol solutions from the mixed TTMAB/SDS system with different molar ratios and various concentrations of cholesterol. The drug release measurements for arbutin were carried out for 24 h. Physical properties of the vesicles were studied by techniques of dynamic light scattering, fluorescence polarization, and transmission electron microscopy (TEM). Encapsulation efficiency and release rate of the vesicles for arbutin were analysed by high-performance liquid chromatography (HPLC). The results showed that the size of the vesicles was not significantly changed by increasing the cholesterol content. However, increasing the ethanol concentration seemed to reduce the vesicle size. In addition, increasing the cholesterol concentration would increase the vesicular bilayer rigidity and enhance the physical stability of the vesicles. The TEM images confirmed that the vesicles possessed spherical structures. The most stable vesicles were found for the TTMAB/SDS mixture with a molar ratio of 3/7 and a cholesterol content of 3 mM or 4 mM in an aqueous phase containing 10 vol.% ethanol. The lifetime of the vesicles was more than 300 days without a significant change in size.
    The stable catanionic vesicles were demonstrated to be able to encapsulate model drugs, vitamin E acetate and arbutin, respectively, confirming that the TTMAB/SDS vesicles possessed bilayer structures. Encapsulation efficiency of the TTMAB/SDS (molar ratio 3/7) vesicles with 3 mM or 4 mM cholesterol was decreased by increasing the VEA concentration due to the limitation space in the hydrophobic regions of the vesicular bilayers. However, the vesicles fabricated with 3 mM cholesterol had higher encapsulation efficiency than that fabricated with 4 mM cholesterol due to the competing effect between cholesterol and VEA in the vesicular bilayers. The results showed that the vesicle size had a positive correlation with the encapsulation efficiency for arbutin. That is, the smaller the vesicle size, the less the arbutin encapsulated. At 30 vol.% ethanol, arbutin was released up to 80% after 24 h. By fitting the release curve to kinetic models, it is found that the release behaviour of the TTMAB/SDS (molar ratio 3/7) vesicles with 3 mM cholesterol followed the Higuchi model at 10 vol.% and 20 vol.% ethanol and followed the first order model at 30 vol.% ethanol. In the other hand, the TTMAB/SDS (molar ratio 3/7) vesicles with 4 mM cholesterol at 10 vol.% ethanol followed the first order model. In addition, increasing the ethanol concentration would increase the bilayer fluidity and thus the drug release rate.

    ABSTRACT I ACKNOWLEDGEMENT III LIST OF TABLES VIII LIST OF FIGURES IX LIST OF SYMBOLS XII CHAPTER I INTRODUCTION 1 1.1. Background 1 1.2. Research Motivation 3 CHAPTER II LITERATURE REVIEW 5 2.1 Catanionic Vesicles 5 2.2. Packing Parameter 7 2.3. Phase Behavior 11 2.4 Effect of Cholesterol 13 2.5 Effect of Ethanol 15 2.6 Drug Release Behavior 16 CHAPTER III EXPERIMENTAL 24 3.1. Materials 24 3.2 Equipment 24 3.2.1. Homogenizer 24 3.2.2. Particle Size/ Zeta Potential Analyzer 25 3.2.3. Laser Doppler Electrophoresis Zeta Potential Analyzer 26 3.2.4. Transmission Electron Microscope 28 3.2.5. Fluorescence Spectrometer 29 3.2.6. Gel Chromatography Column 30 3.2.7. High Performance Liquid Chromatography 31 3.3 Methodology 31 3.3.1. Preparation of Catanionic Vesicles 31 3.3.2. Size Distribution of Catanionic Vesicles 34 3.3.3. Zeta Potential of Catanionic Vesicles 34 3.3.4. Transmission Electron Microscope Observation 34 3.3.5. Fluorescence Polarization Measurement 35 3.3.6. High performance liquid chromatography 36 3.3.7. In Vitro Drug Release Measurement of Arbutin 38 CHAPTER IV RESULTS AND DISCUSSION 40 4.1 Physical Properties of Catanionic Vesicles 40 4.2 Phase Transition of the Bilayer Structures in TTMAB/SDS Catanionic Vesicles 49 4.3 Encapsulation of Vitamin E Acetate 55 4.4 Encapsulation of Arbutin 62 4.5 Drug Release Behavior of Arbutin 67 CONCLUSIONS 72 REFERENCES 74

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