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研究生: 洪偉邦
Ang, Ivan Antony
論文名稱: 含對稱雙十二碳鏈離子對雙親分子及帶負電脂質之陰陽離子液胞的物理穩定性及維他命E醋酸酯包覆效率
Physical stability and vitamin E acetate encapsulation efficiency of catanionic vesicles containing symmetric dodecyl-chained ion pair amphiphile and anionic lipid
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: 2011
畢業學年度: 99
語文別: 英文
論文頁數: 94
中文關鍵詞: 陰陽離子液胞包覆效率離子對雙親分子維他命E
外文關鍵詞: catanionic vesicle, encapsulation efficiency, ion pair amphiphile, vitamin E acetate
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  • 在本研究中,先成功製備出以陰離子型界面活性劑 sodium dodecylsulfate (SDS)與陽離子型界面活性劑dodecyltrimethylammonium bromide (DTMAB) 所組成之離子對雙親分子 (ion pair amphiphile, IPA) DTMA-DS。然後利用強制性製程由此離子對雙親分子製備出陰陽離子液胞,並探討添加雙十六碳鏈磷酸鹽及膽固醇對於液胞物理穩定性及包覆效率的影響。針對包覆實驗,嘗試將疏水性的維他命E醋酸酯包覆於液胞中,其包覆量則以HPLC搭配UV偵測器進行分析,還利用螢光偏極化技術探討液胞雙層膜的排列特性。
    陰陽離子液胞的物理穩定性是由室溫下外觀、粒徑與表面電位隨時間的變化加以判定。陰陽離子液胞的平均粒徑分布在56到98 nm之間,且分布很窄,而液胞的帶負電特性可由-44到-67 mV的界面電位值加以證實。膽固醇的添加在穩定之DTMA-DS/DHDP液胞的生成上扮演關鍵的角色。 研究發現雙十六碳鏈磷酸鹽則提供陰陽離子液胞的帶負電特性,而誘導出液胞間的靜電排斥作用,得以抑制液胞間的融合或聚集。穿透式電子顯微鏡影像則顯示液胞的球狀結構。
    含膽固醇之陰陽離子液胞包覆維他命E醋酸的酯效率,依序為 35 mol%> 43 mol% > 50 mol%膽固醇,且隨雙十六碳鏈磷酸鹽之莫耳分率的增加,其包覆效率隨之下降。雙十六碳鏈磷酸鹽與膽固醇的添加會影響陰陽離子液胞雙層膜的性質,並發現維他命E醋酸酯的包覆會促進陰陽離子液胞的穩定性。此外,含對稱碳氫鏈之DTMA-DS (C12-C12)的液胞包覆效率較含非對稱性碳氫鏈之hexadecyltrimethylammonium-dodecylsulfate (HTMA-DS) (C16-C12) 的液胞低,但其差異性不是很明顯。

    In this study, successful formation of ion pair amphiphile (IPA), dodecyltrimethylammonium-dodecylsulfate (DTMA-DS), composed of anionic surfactant, sodium dodecylsulfate (SDS), and cationic surfactant, dodecyltrimethylammonium bromide (DTMAB), was carried out. Catanionic vesicles were then prepared from the IPA with a forced formation approach. The effects of added dihexadecyl phosphate (DHDP) and cholesterol on the stability and encapsulation efficiency of the catanionic vesicles were evaluated. For the encapsulation experiments, vitamin E acetate as a hydrophobic material was tried to be encapsulated within the catanionic vesicles. The amount of vitamin E acetate was measured by HPLC with UV detector, and fluorescence polarization study was performed to investigate the bilayer packing characteristics of the vesicles.
    Physical stability of the catanionic vesicles determined by visual, vesicle size, and zeta potential values was monitored with time at room temperature. The mean sizes of the vesicles ranged from 56 to 98 nm with narrow size distributions. Negatively charged characteristic of the vesicles was confirmed based on the zeta potential values varying from -44 to -67 mV. The incorporation of cholesterol was found to be critical in the formation of stable DTMA-DS/DHDP catanionic vesicles. DHDP was found to provide a negatively charged characteristic for the catanionic vesicles, which induced the repulsive interaction between vesicles and thus inhibited the fusion or aggregation of the vesicles. Transmission electron microscopy (TEM) images showed the spherical structures of the vesicles.
    The encapsulation efficiency values of the catanionic vesicles containing cholesterol for vitamin E acetate were followed the order of 35 mol% > 43 mol% > 50 mol% cholesterol in the vesicles. It was also observed that increasing the molar fraction of DHDP led to the lower encapsulation efficiency for vitamin E acetate. Incorporation of DHDP and cholesterol could affect the bilayer properties of the catanionic vesicles. Encapsulation with vitamin E acetate was found to increase the stability of the catanionic vesicles. In addition, vesicles containing DTMA-DS (C12-C12) with symmetry hydrocarbon chains had lower encapsulation efficiency for vitamin E acetate than that of vesicles containing hexadecyltrimethylammonium-dodecylsulfate, HTMA-DS (C16-C12), but the difference is not obvious.

    ABSTRACT i 摘要 iii ACKNOWLEDGEMENT v Table of Contents vii List of Tables ix List of Figures x CHAPTER 1 INTRODUCTION 1 CHAPTER 2 LITERATURE REVIEW 3 2.1 Ion pair amphiphile 3 2.2 Formation of catanionic vesicles 6 2.3 Charged vesicles 7 2.4 Effect of cholesterol 9 2.5 Encapsulation of vitamin E acetate 11 CHAPTER 3 EXPERIMENTAL 19 3.1 Materials 19 3.2 Equipments 19 3.2.1 Ultrasonic dispersion device 19 3.2.2 Dynamic light scattering particle size analyzer 20 3.2.3 Laser doppler electrophoresis zeta potential analyzer 21 3.2.4 Transmission electron microscope 22 3.2.5 High performance liquid chromatography instrument 23 3.2.6 Multi-mode microplate reader 23 3.3 Methodology 24 3.3.1 Preparation of DTMA-DS 24 3.3.2 Preparation of catanionic vesicles 25 3.3.3 Size distribution of catanionic vesicles 25 3.3.4 Zeta potential of catanionic vesicles 26 3.3.5 Transmission electron microscope observation 26 3.3.6 Evaluation of vitamin E encapsulation efficiency 27 3.3.7 Fluorescence polarization measurement 28 CHAPTER 4 RESULTS AND DISCUSSION 33 4.1 Formation of catanionic vesicles 33 4.1.1 Catanionic vesicles formed by DTMA-DS 33 4.1.2 Catanionic vesicles formed by DTMA-DS/DHDP 35 4.1.3 Catanionic vesicles formed by DTMA-DS/DHDP/cholesterol 37 4.2 Vitamin E acetate encapsulation with catanionic vesicles 43 4.2.1 Properties of drug-loaded catanionic vesicles formed by DTMA-DS/DHDP/Cholesterol 44 4.2.2 Separation of vitamin E acetate-loaded vesicles and non-encapsulated vitamin E acetate 46 4.2.3 Encapsulation efficiency for vitamin E acetate 47 CHAPTER 5 CONCLUSIONS 79 REFERENCES 81 CURRICULUM VITAE 94

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