本研究首先製備DeTMA-DS ( decyltrimethylammonium- dodecylsulfate )、DeTMA-TS (decyltrimethylammonium-tetradecylsulfate) 和DTMA-DS (dodecyltrimethylammonium-dodecylsulfate)三種陰陽離子界面活性劑（catanionic surfactant）做為三種液胞的主材料，並應用乙醇的共溶劑效應，採用半自發製程，在緩衝溶液(tris buffer)中製備陰陽體(catansomes)。探討乙醇、膽固醇的濃度對陰陽體粒徑、界面電位及物理穩定性的影響。本研究並進一步以維他命E醋酸酯(dl-α-tocopheryl acetate, VEA)做為被包覆物，探討陰陽體對油溶性藥物的包覆行為。
實驗結果顯示，添加適當濃度的乙醇可以有效促進DeTMA-TS與DeTMA-DS陰陽體的物理穩定性，20%的乙醇具有最好的效果。此外，膽固醇的添加對於此兩種陰陽體皆可以更進一步的提昇其穩定性。但對於DTMA-DS系統而言，單獨乙醇並無法促成穩定陰陽體的形成，只有在適量膽固醇添加(6mM)下才有較好的穩定性。在包覆油溶性藥物維生素E醋酸酯行為的研究上，對於DeTMA-TS與DeTMA-DS系統而言，包覆效率隨著膽固醇含量的增加而增大; 但對於DTMA-DS系統而言，包覆效率則隨著膽固醇含量的增加而減小。究其原因，可由差示掃描熱卡計（differential scanning calorimetry）以及螢光偏極化(Fluorescence Polarization)的實驗結果顯示三種陰陽離子界面活性劑的雙層膜相轉移溫度不同，而膽固醇的添加對於雙層膜的流動性造成相反的影響所致。

The stable catansomes were prepared from catanionic surfactants (DeTMA-TS , DeTMA-DS and DTMA-DS) in the presence of ethanol by a semispontaneous process. A systematic study can be researched the effects of ethanol and cholesterol concentrations with different materials on the size, zeta-potential, and physical stability in tris buffer solution. Furthermore, the catansomes were used to encapsulate oil-soluble drug such as vitamin E acetate.Then the encapsulation behavior of catansomes can be researched.
The experimental results suggest a optimal 20%v/v ethanol and more cholesterol concentration was found to enhance stability of vesicles for DeTMA-TS and DeTMA-DS systems. However , for DTMA-DS system , a suitable cholesterol concentration was found optimum stability. The membrane fluidity results clearly indicated that more cholesterol concentration increased rigidity above the phase transition temperature for DeTMA-TS and DeTMA-DS systems and decreased rigidity below the phase transition temperature for DTMA-DS system. For encapsulating oil-soluble drug , the encapsulation efficiency of catansomes are depended on membrane rigidity, indicating that more membrane rigidity can get higher encapsulation efficiency.

參考文獻
Antonietti, M. and Főrter, S., “Vesicles and liposomes : A self-assembly principle beyond lipid, ” Advanced Materials 15, 1323-1333, 2003.
Abu, A.S., Kizuki, S., Doi, Y., Suzuki, T., Ishida, T. and Kiwada, H., “Oxaliplatin encapsulated in PEG-coated cationic liposomes induces significant tumor growth suppression via a dual-targeting approach in a murine solid tumor model,” Journal of Controlled Release 137, 8-14, 2009.
Ahmad, I., Longenecker, M., Samuel, J. and Allen, T. M., “Antibody-targeted delivery of doxorubicin entrapped in sterically stabilized liposomes can eradicate lung cancer in mice,” Cancer Research 53, 1484-1487, 1993.
Anais, J. P., Razzouq, N., Carvalho, M., Fernandez, C., Astier, A., Paul, M., Fessi, H. and Lorino, A. M., “Development of alpha-tocopherol acetate nanoparticles: influence of Preparative Processes,” Drug Development and Industrial Pharmacy 35, 216-223, 2009.
Barry, J. A. and Gawrisch, K., “Direct NMR evidence for ethanol binding to the lipid-water interface of phospholipid bilayers,” Biochemistry 33, 8082-8088, 1994.
Bradford, A., Atkinson, J. and Fuller, N., “The effect of vitamin E on the structure of membrane lipid assemblies,” Lipid Research 44, 2003.
Bramer, T., Paulsson, M., Edwards, K. and Edsman, K. “Catanionic drug-surfactant Mixtures: Phase Behavior and Sustained Release from Gels, ” Pharmaceutical Research 20, 10, 2003.
Brown, M. F., Thurmond, R. L.., Dodd, S. W., Otten, D. and Beyer, K., “Elastic deformation of membrane bilayers probed by deuterium NMR relaxation,” J. Am. Chem. Soc. 124, 8471-8484, 2002.
Bin, X. and Lipkowski, J., “Electrochemical and PM-IRRAS studies of the effect of cholesterol on the properties of the headgroup region of a DMPC bilayer supported at a Au(111) electrode,” J. Phys. Chem. B 110, 26430-26441, 2006.
Bucak, S., Robinson, B. H. and Fontana, A., “Kinetics of induced vesicle breakdown for cationic and catanionic systems,” Langmiur 18, 8288-8292, 2002.
Bhattacharya, S., and Haldar, J., “Interactions between cholesterol and lipids in bilayer membranes. Role of lipid headgroup and hydrocarbon chain-backbone linkage,” Biochim. et Biophys. Acta 1467, 39-53, 2000.
Brigelius-Flohe, R. and Traber, M.G., “Vitamin E: function and metabolism,” FASEB J. 13, 10,1145–1155,1999.
Bhardwaj, U.and Burgess, J.D.,“Physicochemical properties of extruded and non-extruded liposomes containing the hydrophobic drug dexamethasone2010,” Pharmaceutics, 388, 181-189, 2010.
Cevc, G. and Blume, G., “Lipid vesicles penetrate into intact skin owing to the transdermal osmotic gradients and hydration force,” Biochim. Biophys. Acta. 1104, 226-232, 2003.
Cevc, G., “Hydration force and the interfacial structure of the polar surface,” J. Chem. Soc., Faraday Trans. 87, 2733-2739, 1991.
Chien, C. L., Yeh, S. J., Yang, Y. M., Chang, C. H. and Maa. J. R., “Formation and encapsulation of catanionic vesicles,” J. Chin. Colloid & Interface Soc. 24, 31-45, 2002.
Chanturiya, A., Leikina, E., Zimmerberg, J. and Chernomordik, L. V., “Short-Chain Alcohols Promote an Early Stage of Membrane Hemifusion,” Biophysical J. 77, 2035-2045, 1999.
Coldren, B. A., Warriner, H., Zanten R. V., Zasadzinski, J. A. and Sirota, E. B., “Flexible bilayers with spontaneous curvature lead to lamellar gels and spontaneous vesicles,” PNAS 103, 2524-2529, 2006.
Chung, Y. C. and Regen, S. L., “Comparision of barrier properties of bilayers derived from an ion-paired amphiphile with those of a phosphatidylcholine analog,” Langmuir 8, 2843-2845, 1992.
Chung, Y. C.,Lee, H. J.,and Park, J. Y., “Bilayer properties of the multiple-chain ion-pair amphiphiles,” Bull. Korean Chem. Soc. 19, 1249-1252, 1998.
Clares,B. Gallardo,V., Medina,M.M. and Ruiz,M., “Multilamellar liposomes of triamcinolone acetonide: preparation, stability, and characterization,” Liposome Research 19, 197–206, 2009.
Deme´, B., Dubois, M. and Zemb, T., “ Swelling of a lecithin lamellar phase induced by small carbohydrate solutes,” Biophysical J. 82, 215-225, 2002.
Duclairoir, C., Orecchioni, A. M., Depraetere, P. and Nakache, E., “Alpha-tocopherol encapsulation and in vitro release from wheat gliadin nanoparticles,” J. Microencapsulation 19, 53-60, 2002.
Elsayed, M. M. A., Abdallah, O. Y., Naggar, V. F. and Khalafallah, N. M., “Lipid vesicles for skin delivery of drugs: Reviewing three decades of research,” Int. J. Pharmaceutics 322, 1-16, 2007.
Evans, E. and Needham, D., “Physical properties of surfactant bilayer membranes: thermal transitions, elasticity, rigidity, cohesion and colloidal interactions,” J. Phys. Chem. 91, 4219-4228, 1987.
El-Nesr, O. H., Yahiya, S.A. and El-Gazayerly, O.N., “Effect of formulation design and freeze-drying on properties of fluconazole multilamellar liposomes,” Saudi Pharmaceutical 18, 217-224, 2010.
Fukuda, H., Kawata, K. and Okuda, H., “Bilayer-forming ion-pair amphiphiles from single-chain surfactants,” J. Am. Chem. Soc. 112, 1635, 1990.
Gallarate, M., Chirio, D., Trotta, M. and Carlotti, M. E., “Deformable liposomes as Topical Formulations Containing a-Tocopherol,” Dispersion Science and Technology 27, 703–713, 2006.
Gonnet, M., Lethuaut, L. and Boury, F., “New trends in encapsulation of liposoluble vitamins,” Controlled Release146, 276-290, 2010.
Grasso, D., Subramaniam1, K., Butkus, M., Strevett, K.and Bergendah, J., “A review of non-DLVO interactions in environmental colloidal systems,” Reviews in Environmental Science & BioTechnology 1, 17-38, 2002.
Hao, Y.M. and Li, K., “Entrapment and release difference resulting from hydrogen bonding interactions in niosome,” Pharmaceutics, 245-253 , 2011.
Hargeaves, W. R. and Deamer, D. W., “Liposomes from ionic,single chain amphiphiles,” Biochemistry 17,3759-3768, 1978.
Huang, J. B. and Zhao, G. X., “Formation and coexistence of the micelles and vesicles in mixed solution of cationic and anionic surfactant,” Colloid Polym. Sci. 273, 156-164, 1995.
Huang, J. B., Zhu, B. Y., Zhao, G. X. and Zhang, Z. Y., “Vesicle formation of a 1:1 cationic surfactant mixture in ethanol solution,” Langmuir 13, 5759-5761, 1997.
Huang, J. B., Zhu, B. Y., Mao, M., He, P., Wang, J. and He, X., “Vesicle formation of 1:1cationic and anionic surfactant mixtures in nonaqueous polar solvents,” Colloid Polym. Sci. 277, 354-360, 1999.
Hincha, D. K., “Effects of alpha-tocopherol (vitamin E) on the stability and lipid dynamics of model membranes mimicking the lipid composition of plant chloroplast membranes,” Federation of European Biochemical Societies Letters 582, 25-26, 3687-3692, 2008.
Israelachvili, J. N., “Intermolecular and surface forces,” 2nd Ed., Academic, New York, 1992.
Jesorka, A. and Orwar O., “Liposomes: technologies and analytical applications,” Annu. Rev. Anal. Chem. 27, 1-32, 2008.
Kaler, E. W., Murthy, A. K., Rodriguez, B. E. and Zasadzinski, J. A. M., “Spontaneous vesicle formation from aqueous mixtures of single-tailed surfactants,” Science 245, 1371-1374, 1989.
Lasic, D. D.,“Novel applications of liposomes,”1998.
Li, S., Lin H., Wang G. and Huang C., “Effects of alcohols on the phase transition temperatures of mixed-chain phosphatidylcholines,” Biophysical J. 70. 2784-2794, 1996.
Ly, H. V., Block, D. E. and Longo, M. L., “Interfacial tension effect of ethanol on lipid bilayer rigidity, stability, and area/molecule: a micropipette aspiration approach,” Langmuir 18, 8988-8995, 2002.
L´opez, O., Mazaa, A. D. D., Codercha, L., L´opez- Iglesiasb, C., Wehrlic, C. E. and Parra, J. L., “Direct formation of mixed micelles in the solubilization of phospholipid liposomes by Triton X-100,” Federation of European Biochemical Societies Letters 426, 314-318, 1998.
Liu, N. and Park, H.J., “Chitosan-coated nanoliposome as vitamin E carrier,” J. Microencapsulation 26, 235–242, 2009.
L´opez-Pinto,J.M., Gonz´alez-Rodr´ıguez,M.L. and Rabasco,A.M., “Effect of cholesterol and ethanol on dermal delivery from DPPC liposomes,” Pharmaceutics, 1-12, 2005.
Mizoguchi, H. and Hara, S., “Effect of fatty acid saturation in membrane lipid bilayers on simple diffusion in the presence of ethanol at high concentrations,” J. Fermentation and Bioenfgineering 81, 406-411, 1996.
McIntosh, T. J., Magid, A. D. and. Simons, S. A., “Cholesterol modifies the short-range repulsive interactions between phosphatidylcholine membranes,” Biochemistry 28, 17-25, 1989.
Mustafa, M. A., Ossama, Y., and Viviane, F., “Lipid vesicles for skin delivery of drugs：Reviewing three decades of research,” International Journal of Pharmaceutics 332, 1–16, 2007.
Malam., Y., Loizidou, M., and Seifalian, A. M., “Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer,” Trends in Pharmacological Sciences 30, 11, 2009.
McIntosh, T. J., Lin H., Li S. and Huang C. H., “The effect of ethanol on the phase transition temperature and the phase structure of monounsaturated phosphatidylcholines,” Biochim. Biophys. Acta, 1510, 219-230, 2001.
Margus, R.V.and James,H.D.,“Phase equilibria of cholesterol/dipalmitoylphosphatidylcholine Mixtures: 2H Nuclear Magnetic Resonance and Differential Scanning Calorimetry,” Biochemistry, 29, 45 1-464, 1990.
McMullen, T. P. W., Lewis, R. N. A. H. and McElhaney, R. N., “Differential scanning calorimetric and fourier transform infrared spectroscopic studies of the effects of cholesterol on the thermotropic phase behavior and organization of a homologous series of linear saturated phosphatidylserine bilayer membranes,” Biophysical Journal 79, 2056-2065, 2000.
Mao, M., Huang, J. B., Zhu, B. Y., Yin., H. Q. and Fu, H. L., “ The structural transition of catanionic vesicles induced by toluene,” Langmuir 18, 3380-3382, 2002.
McLaughlin, A., Vaio, W. K., Wilson, G. T. and McLaughlin, S., “Dimethonium, a divalent cation that exerts only a screening effect on the electrostatic potential”, J. Membrane Biol. 76, 183-193, 1983.
McIntosh, T. J., Kulkarni, K. G. and Simon, S. A., “Membrane fusion promoters and inhibitors have contrasting effects on lipid bilayer structure and undulations,” Biophysical J. 76, 2090-2098, 1999.
McMullen, T. P. W., Lewis, N. A. H. and McElhaney, R. N., “Differential scanning calorimetric study of the effect of cholesterol on the thermotropic phase behavior of a homologous series of linear saturated phosphatidylcholines,” Biochemistry 32, 516-522, 1993.
McMullen, T. P. W., Lewis, R. N. A. H. and McElhaney, R. N., “Calorimetric and spectroscopic studies of the effects of cholesterol on the thermotropic phase behavior and organization of a homologous series of linear saturated phosphatidylglycerol bilayer membranes,” Biochimica et Biophysica, 345-357, 2009.
Manosroi, A., Wongtrakul, P., Manosroi, J., Sakai, H., Sugawara, F., Yuasa, M. and Abe, M., “Characterization of vesicles prepared with various non-ionic surfactants mixed with cholesterol,” Colloids and Surfaces B-Biointerfaces, 30, 129-138, 2003.
New, R. R. C.(Ed.), “Liposomes: A practical approach,” Oxford University Press, New York, 1990.
Patra, M., Salonen, E., Terama, E.,Vattulainen, I., Faller, R., Lee,B. W., Holopainen, J. and Karttunen, M.,” Under the influence of alcohol: the effect of ethanol and methanol on lipid bilayers,” Biophysical J. 90, 1121-1135, 2006.
Petrache, H. I., Zemb, T., Belloni, L. and Parsegian, V. A., “Salt screening and specific ion adsorption determine neutral-lipid membrane interactions,” PNAS 103, 7982-7987, 2006.
Padamwar, M.N. and Pokharkar, V.B., “Development of vitamin loadedtopical liposomal formulation using factorial design approach: Drugdeposition and stability,” International Journal of Pharmaceutics, 320, 37–44, 2006.

Shin, Y.J., Park, C.S., Lee, C.I. and Shin, J.S., “Preparation and characterization of vesicles using octasubstituted cyclotetraphosphazene,” Bull. Korean Chem. Soc. 29, 10, 2008.
Silva, C., Aranda, F.J., Ortiz, A., Martinez, V., Carvajal, M. and Teruel, J.A., “Molecular aspects of the interaction between plants sterols and DPPC bilayers an experimental and theoretical approach,” Colloid and Interface Science, 192-201, 2011.
Srivastava, S., Phadke, R.S. , Govil, G. Rao, C.N.R., “Fluidity, permeability and antioxidant behaviour of model membranes incorporated with [alpha]-tocopherol and vitamin E acetate,” Biomembranes 734, 353–362, 1983.
Stokes, R. J. and Evans, D. F.,“Fundamentals of Interfacial Engineering,” Wiley-VCH, Inc., New York, 1997.
Tan, M.L., Choong P.F.M. and Dass C.R.. “Recent developments in liposomes, microparticles and nanoparticles for protein and peptide drug delivery,” Peptides 31, 184–193, 2010.
Torchilin, V. P., “Recent advances with liposomes as pharmaceutical carriers,” Nature Reviews Drug Discovery 4, 145-160, 2005.
Tondre, C. and Caillet, C., “Properties of the amphiphilic films in mixed cationic/anionic vesicles: a comprehensive view from a literature analysis,” Advances in Colloid and Interface Science 93, 115-134, 2001.
Touitou, E., Dayan, N., Bergelson, L., Godin, B. and Eliaz, M., “Ethosomes – novel vesicular carriers for enhanced delivery:characterization and skin penetration properties,” J. Control., 403-418, 2000.
Vanegas, J.M., Faller,R.and Longo,M.L., “Influence of Ethanol on Lipid/Sterol Membranes: Phase DiagramConstruction from AFM Imaging,” Langmuir 26, 10415–10418, 2010.
Wang, C. Z., Tang, S. H., Huang, J. B., Zhang, X. R. and Fu, H. L., “Transformation from precipitates to vesicles in mixed cationic and anionic surfactant systems”, Colloid Polym. Sci. 280, 770-774, 2002.
Walz, J. Y. and Ruckenstein, E., “Comparison of the van der waals and undulation interactions between uncharged lipid bilayers,” J. Phys. Chem. B 103, 7461-7468, 1999.
Weinstein, J.N., Yoshikami, S., Henkat, P., Blumenthal, R. and Hagins, W. A., “Liposome-cell interaction: transfer and intracellular release of a trapped fluorescent marker,” Science 195, 489-492, 1977.
Weinstein, J.N., Ralston, E., Leserman, L.D., Klausner, R.D., Dragsten, P., Henkart, P. and Blumenthal, R., “Self-quenching of carboxyfluorescein: uses in studying liposome stability and liposome-cell interaction,” in Liposome TechnologyL Targeted Drug Delivery and Biological Interaction, G. Gregoriadis, Ed., CRC, Boca Raton, 1984.
Wu, K. C., Huang, Z. L., Yang, Y. M., Chang, C. H., and Chou, T. H., “Enhancement of catansome dormation by means of cosolvent effect: Semi-spontaneous preparation method,” Colloids and Surfaces A: Physicochem. Eng. Aspects 302, 599-607, 2007.
Xi, J., Guo, R.and Guo, X., “Interactions of hemoglobin with lecithin liposomes”, Colloid and Polymer Science 284, 1139-1145, 2007.
Yang, Y. M., Wu, K. C., Huang, Z. L. and Chang, C. H., “On the stability of liposomes and catansomes in aqueous alcohol solutions,” Langmuir 24, 1695-1700, 2008.
Yu, W. Y., Yang, Y. M., Chang, C. H., “Cosolvent effects on the spontaneous formation of vesicles from 1:1 anionic and cationic surfactant mixtures,” Langmuir 21 6185-6193, 2005.
Zeng, J., Smith K. E., and Chong P. L., “Effects of alcohol-induced lipid interdigitation on proton permeability in L-a-dipalmitoylphosphatidylcholine vesicles,” Biophysical J. 65, 1404-1414, 1993.
Zhang, X. R., Huang, J. B., Mao, M., Tang, S. H. and Zhu, B. Y., “From precipitation to vesicles: a study on self-organized assemblies by alkylammonium and its mixtures in polar solvents,” Colloid Polym. Sci. 279, 1245-1249, 2001.
Zigoneanu, I. G., Astete, C. E., Sabliov, C. M., “Nanoparticles with entrapped alpha-tocopherol: synthesis, characterization, and controlled release,” Nanotechnology19, 10, 0957-4484, 2008.
歐陽鐘汕和劉寄星，「從肥皂泡到液晶生物膜」，新世紀物理研習叢書9，牛頓出版(台灣)，1995。
陳炳宏和馮思慎，「微脂粒在藥物輸送的應用」，中國化學工程學會會刊，47(3)，68-84，2000。
鍾依玲，「陰/陽離子液胞自發性形成之探討」，國立成功大學化學工程學系碩士論文，2002。
徐立銘，「陰陽離子液胞包覆行為之探討」，國立成功大學化學工學系碩士論文,2002.
劉晏如，「微脂粒配方與血液中蛋白質交互作用及其穩定性之研究」，國立清華大學化學工程學系碩士論文，2002。　
李雅鈺，「含膽固醇之陰陽離子液胞穩定性及包覆行為之研究」， 國立成功大學化學工程學系碩士論文,2004。
吳國彰，「陰陽離子液胞穩定性及包覆/釋放行為的研究」，國立成功大學化學工程學系碩士論文，2005。
黃鉦琳，「帶電陰陽離子液胞的形成及其膠化之研究」， 國立成功大學化學工程學系碩士論文，2007。
柯政遠，「乙醇體及陰陽體的製備及其包覆釋放行為之探討」，國立成功大學化學工程學系碩士論文，2008。
李威漢，「陰陽離子界面活性劑的製備及其相轉移行為的熱卡分析」，國立成功大學化學工程學系碩士論文，2010。