本文中製備DTMA‧DS、TTMA‧DS及HTMA‧DS三種具有不同碳鏈對稱性的離子對雙親分子（IPA），並利用製膜、超音波振盪及擠壓等一系列程序，在水中將其形成陰陽離子液胞。由於強制性形成的陰陽離子液胞普遍存在穩定性不佳的問題，本文首次嘗試使用甲醇、乙醇、正丙醇和正丁醇等醇類共溶劑，探討醇類共溶劑的添加對陰陽離子液胞穩定性的影響。液胞的穩定性主要是依據粒徑的測量及目視觀察的綜合判斷，另外也利用濁度測量及TEM的顯微觀測作為輔助。

實驗結果顯示本文所探討的共溶劑種類、添加量及IPA碳鏈對稱性等三個參數對陰陽離子液胞穩定性的影響中，以IPA碳鏈對稱性的影響最大。碳鏈對稱的IPA可經由正丙醇及正丁醇的適量添加大幅促進其穩定性，可望達到實用目標。此外，本文亦根據溶劑的介電效應提出影響陰陽離子液胞穩定性的可能機制，並合理地解釋本研究的實驗結果。根據此一機制，隨著共溶劑的添加，水溶液的介電常數遞減，陰陽離子界劑的兩個具相反電性的親水頭基間的靜電作用力因而增強，有利於以液胞的狀態存在。但另一方面，陰陽離子界劑的兩條疏水尾基的疏水效應也因而減弱，有利於以單分子的狀態存在。在這兩個相反作用的相抗衡下，首先前者凌駕後者，促進液胞的穩定性。但隨著共溶劑添加量持續增加，後者反而逐漸凌駕前者，造成液胞的穩定性降低，更進而完全溶解，以單分子的狀態存在。

Three ion pair amphiphiles (IPAs), derived from a series of alkyl trimethyl ammonium chlorides and sodium dodecyl sulfate, were used to form catanionic vesicles in water upon mechanical dispersion method. For the first time in the literature, short-chained alcohols (methanol, ethanol, n-propanol, and n-butanol) were added as cosolvents and studied systematically for their effects on the stability of the ensuing vesicles.

Dynamic light scattering measurements indicated that one of the IPAs (i.e. DTMA‧DS) can be efficiently and successfully stabilized by the addition of suitable amounts of n-parpanol and n-butanol. More than three months storage period for stable vesicles was observed and this demonstrates that a novel method for stabilization of catanionic vesicles becomes available by means of cosolvent addition. Moreover, an explanation based on the medium dielectric effect was proposed. According to this mechanism, cosolvent addition may affect both the interaction between hydrophilic groups and that between the hydrophobic groups of the IPAs. With decreasing the dielectric constant of the mixed solvent by increasing the concentration of the cosolvent, the attractive interaction between polar groups will be strengthened on one hand the solvophobic effect of hydrophobic groups will be weaken on the other hand. These two opposite effects counterbalance each other and result in variations of vesicle stability with cosolvent concentration.

Amante, J. C.; Scamehorn, J. F.; Harwell, J. H., “Precipitation of mixtures of anionic and cationic surfactants: effect of surfactant structure, temperature, and pH,” J. Colloid Interface Sci. 1991. 144, 243.

Adachi, T.; Takahashi, H.; Ohki, K.; Hatta, I., “Interdigitated structure of phospholipid-alcohol systems syudied by X-Ray diffraction,” Biophys. J., 1995, 68, 1850.

Alder-Moore, J. P.; Proffitt, R. T., “Development, characterization, efficacy and mode of action of AmBisome, a unilamellar liposomal formulation of amphotericin B.,” J. Liposome Res. 1993, 3, 429.

Armengol, X.; Estelrichl, J., “Physical stability of different liposome compositions obtained by extrusion method,” J. Microencapsulation 1995, 12, 525.

Ashbaugh, H. S.; Boon, K.; Prud’homme, R. K., “Gelation of catanionic vesicles by hydrophobically modified polyelectrolytes,” Colloid Polym. Sci. 2002, 280, 783.

Barry, J. A.; Gawtisch, K., “Direct NMR evidence for ethanol binding to the lipid-water interface of phospholipid bilayers,” Biochemistry 1994, 33, 8082.

Bergstro"m, M.; Pedersen, J. S.; Schurtenberger, P.; Egelhaaf, S. U., “Small-Angle Neutron Scattering (SDNS) Study of Vesicles and Lamellar Sheets Formed from Mixtures of an Anionic and a Cationic Surfactant,” J. Phys. Chem. 1999, 103, 9888.

Bhattacharya, S.; De, S., “Vesicle formation from dimeric ion-paired amphiphiles. Control over vesicular thermotropic and ion-transport properties as a function of intra-amphiphilic headgroup separation,” Langmuir 1999, 15, 3400.

Blankschtein, D.; Thurston, G. M.; Benedek, G. B., “Phenomenological theory of equilibrium thermodynamic properties and phase separation of micellar solutions,” J. Chem. Phys. 1986, 85, 7268.

Blanzat, M.; Perez, E.; Rico-Lattes, I.; Lattes, A., “Synthesis and anti-HIV activity of catanionic analogs of galactosylceramide,” New J. Chem. 1999, 23, 1063.

Blanzat, M.; Perez, E.; Rico-Lattes, I.; Prome, D.; Prome, J. C.; Lattes, A., “New catanionic glycolipids. 1. synthesis, characterization, and biological activity of double-chain and gemini catanionic analogues of galactosylceramide (galβ1cer),” Langmuir 1999, 15, 589.

Braun-Falco, O.; Kortung, H. C.; Maibach, H. I., (Eds.), “Griesbach conference: liposome dermatics, springer-verlag, berlin, heidelberg,” 1992.

Byden, M. S.; Edlund, H., “Dependence of alkyl chain asymmetry on the phase equilibria of three catanionic surfactant mixtures containing dodecyltrimethylammonium chloride-sodium alkylcarboxylate-water,” Langmuir, 2002, 18, 8309.

Chien, C. L.; Yeh, S. J.; Yang, Y. M.; Chang, C. H.; Maa, J. R., “Formation and encapsulation of catanionic vesicles,” J. Chin. Colloid & Interface Soc., 2002, 24, 31.

Chung, Y. C.; Lee, H. E.; Park, J. Y., “Bilayer properties of the multiple-chain ion pair amphiphiles,” Bull. Korean Chem. Soc. 1998, 19, 1249.

Chung, M. H.; Chung, Y. C., “Polymerized ion pair amphiphile that shows remarkable engancement in encapsulation efficiency and very slow release of fluorescent markers,” Coll. Surf. B 2002, 24, 111.

Crommelin, D. J.; Schreier, H., “Liposomes,” in Colloidal Drug Delivery Systems, J. Kreuter, Ed., Marcel Dekker, New York, 1994.

Dayan, N.; Touitou, E., “Carriers for skin delivery of trihexyphenidyl HCl: ethosome vs. liposomes,” Biomaterials 2000, 21, 1879.

Durvasula, R. V.; Huang, C. H., “Hydrocarbon chain packing and the effect of ethanol on the thermotropic phase behavior of mixed-chain phosphatidylglycerols,” Biochim. Biophys. Acta 1999, 1417, 101.

Fendler, J. H., Membrane Mimetic Chemistry, Wiley, New York, 1982.

Fuller, G. M.; Shields, D., Molecular Basis of Medical Cell Biology, MCGraw-Hill, New York, 1998.

Fukuda, H.; Kawata, K.; Okuda, H., “Bilayer-forming ion-pair amphiphiles from single-chain surfactants,” J. Am. Chem. Soc., 1990, 112, 1635.

Forssen, E. A.; Ross, M. E., “DaunoXome Treatment of Solid Tumors: Preclinical and Clinical Investigations,” J. Liposome Res. 1994, 4, 481.

Grohmann, F. L.; Csempesz, F.; Szogyi, M., “Stabilization of small unilamellar DMPC-liposomes by uncharged polymers,” Colloid Polym. Sci. 1998, 276, 66.

Herrington, K. L.; Kaler, E. W.; Miller, D. D.; Zasadzinski, J. A.; Shivkumar, C., “Phase behavior of aqueous mixtures of dodecyltrimethylammonium bromide (DTAB) and sodium dodecyl sulfate (SDS),” J. Phys. Chem. 1993, 97, 13792.

Hirano, K.; Fukuda, H., “Polymerizable ion-paired amphiphiles,” Langmuir 1991, 7, 1045.

Huang, J. B.; Zhao, G. X., “Formation and coexistence of the micelles and vesicles in mixed solution of cationic and anionic surfactant,” Colloid Polym. Sci. 1995, 273, 156.

Huang, J. B.; Zhu, B. Y.; Zhao, G. X.; Zhang, Z. Y., “Vesicle formation of a 1:1 cationic surfactant mixture in ethanol solution,” Langmuir 1997, 13, 5759.

Huang, J. B.; Zhu, B. Y.; Mao, M.; He, P.; Wang, J.; He, X., “Vesicle formation of 1:1cationic and anionic surfactant mixtures in nonaqueous polar solvent,” Colloid Polym. Sci. 1999, 277, 354.

Israelachvili, J. N. Intermolecular and Surface Forces; Academic, New York, 1992.

Kaler, E. W.; Murthy, A. K.; Rodrihguez, B. E.; Zasadzinski, J. A. M., “Spontaneous vesicle formtion in aqueous mixtures of single-tailed surfactants,” Science 1989, 245, 1371.

Kalusner, R. D.; Kumor, N.; Weinstein, J. N.; Blumenthal, R.; Flavin, M. I., “Interaction of tubulin with phospholipids vesicles. Association with vesicles at the phase transition,” J. Biol. Chem. 1981, 256, 5879.

Kamaya, H.; Kaneshina, S., “Partition equilibrium of inhalation anesthetics and alcohols between water and membranes of phospholipids with varying acyl chain-lengths,” Biochim. Biophys. Acta 1981, 646, 135.

Karp, G., Cell and Molecular Biology, 3th Ed., Wiley, New York, 2002.

Koehler, R. D.; Raghavan, S. R.; Kaler, E.W., “Microstructure and Dynamics of Wormlike Micellar Solutions Formed by Mixing Coationic and Anionic Surfactants,” J. Phys. Chem. B 2000, 104, 11035.

Komatsu, H.; Okada, S., “Ethanol-induced aggregation and fusion of small phosphatidylcholine liposome: participation of interdigitated membrane formation in their processed,” Biochim. Biophys. Acta 1995, 1235, 270.

Kondo, Y.; Uchiyama, H.; Yoshino, N.; Nishiyama, K.; Abe, M., “Spontaneous Vesicle Formation from Aqueous Solutions of Didodecyldimethylammonium Bromide and Sodium Dodecyl Sulfate Mixtures,” Langmuir 1995, 11, 2380.

Lasic, D. D., “Liposome in drug delivery,” in Vesicles, M. Rosoff, Ed., Marcel Dekker, New York, 1996.

Mao, M.; Huang, J. B.; Zhu, B. Y.; Yin, H. Q.; Fu, H. L., “The structural transition of catanionic vesicles induced by toluene,” Langmuir 2002, 18, 3380.

Menger, F. M.; Binder, W. H.; Keiper, J. S., “Cationic surfactants with counterions of glucuronate glycosides,” Langmuir 1997, 13, 3247.

Nagel, N. E.; Cevc, G.; Kirchner, S., “The mechanism of the solute-induced chain interdigitation in phosphatidylcholine vesicles and characterization of the isothermal phase transitions by means of dynamic light scattering,” Biochim. Biophys. Acta 1992, 1111, 263.

Nelson, D. L.; Cox, M. M., “Lehninger Principles of Biochemistry,” 3th Ed., Worth, New York, 2000.

New, R. R. C., “Introduction,” in Liposomes: A Practical Approach, R.R.C. New, Ed., Oxford University Press, New York, 1990.

Patist, A.; Chhabra, V.; Pagidipati, R.; Shah, R.; Shah, D. O., “Effect of chain length compatibility on micellar stability in sodium sulfate/alkyltrimethylammonium bromide solutions,” Langmuir 1997, 13, 432.

Perry, R. H.; Green, D., Perry’s Chemical Engineer’s Handbook, 6th Ed., MCGraw-Hill, New York, 1984.

Ranck, J. L.; Tocanne, J. F., “Choline and acetylcholine induce interdigitation of hydrocarbon chains in dipalmitoylphosphatidylglycerol lamellar phase with stiff chains,” FEBS Lett. 1982, 143, 171.

Rosser, M. F. N.; Lu, H. M.; Dea, P., “Effects of alcohols on lipids bilayers with and without cholesterol: the dipalmitoylphosphatidylcholine system,” Biophys. Chem. 1999, 81, 33.

Regev, O.; Khan, A., “Alkyl chain symmetry effects in mixed cationic-anionic surfactant systems,” J. Colloid Interface Sci. 1996, 182, 95.

Rowe, E. S., “The effect of ethanol on the thermotropic properties of dipalmitoyl-phosphatidylcholine,” Pharmacol 1982, 22, 133.

Rowe, E. S., “Lipid chain length and temperature dependence of ethanol-phosphatidylcholine interactions,” Biochemistry 1983, 22, 3299.

Roy, M. T.; Gallardo, M.; Estelrich, J., “Influence of size on electrokinetic behavior of phosphatidylserine and phosphatidylethanolamine lipid vesicles,” J. Colloid Interface Sci. 1998, 206, 512.

Sakai, H.; Matsumura, A.; Yokoyama, S.; Saji, T.; Abe, M., “Photochemical Switching of Vesicle Formation Using an Azobenzene-Modified Surfactant,” J. Phys. Chem. B 1999, 103, 10737.

Salkar, R. A.; Mukesh, D.; Samant, S. D.; Nabigar, C., “Mechanism of micelle to vesicle transition in cationic-anionic surfactant mixtures,” Langmuir 1998, 14, 3778.

Seredyuk, V.; Alami, E.; Nyde'n, M.; Holmberg, K.; Peresypkin, A. V.; Menger, F. M., “Adsorption of zeitterionic gemini surfactants at the air-water and solid-water interfaces,” Colloids Surf. A 2002, 203, 245.

Slater, J. L.; Huang, C. –H., “Interdigitated bilayer membranes,” Prog. Lipid Res. 1988, 143, 171.

Simon, S. A.; MCIntosh, T. J., “Interdigitated hydrocarbon chain packing causes the biphasic transition behavior in lipid / alcohol suspensions,” Biochim. Biophys. Acta 1984, 773, 169.

So"derman, O.; Herrington, K. L.; Kaler, E. W.; Miller, D. D., “Transition from Micelles to Vesicles in Aqueous Mixtures of Anionic and Cationic Surfactants,” Langmuir 1997, 13, 5531.

Stokes, R. J.; Evans, D. F., “Fundamentals of Interfacial Engineering,” Wiley-VCH, New York, 1997.

Tanford, C., “Micelle,” The hydrophobic effect: formation of micelles and biological membranes, Wiley, New York, 1980.

Touitou, E.; Dayan, N.; Bergelson, L.; Godin, B.; Eliaz, M., “Ethosomes－novel vesicular carriers for enhanced delivery: characterization and skin penetration properties,” J. Controlled Release 2000, 65, 403.

Tondre, C.; Caillet, C., “Properties of the amphiphilic films in mixed cationic/anionic vesicles: a comprehensive view from a literature analysis,” Adv. Colloid Interface Sci. 2001, 93, 115.

Wang, C. Z.; Tang, S. H.; Huang, J. B.; Zhang, X. R.; Fu, H. L., “Transformation from precipitates vesicles in mixed cationic and anionic surfactant systems,” Colloid Polym. Sci. 2002, 280, 770.

Weinstein, J. N.; Kalusner, R. D.; Innerarity, T.; Ralston, E.; Blumenthal, R., ”Phase transition release, a new approach to the interaction of proteins with lipid vesicles: applications to liposomes,” Biochim. Biophys. 1981, 647, 270.

Yeagle, P. L., “Cholesterol and the cell membrane,” Biochim. Biophys. Acta 1985, 822, 267.

Yatcilla, M. T.; Herrington, K. L.; Brasher, L. L.; Kaler, E. W., “Phase behavior of aqueous mixtures of cetyltrimethylammonium bromide (CTAB) and sodium octyl sulfate (SOS),” J. Phys. Chem. 1996, 100, 5874.

Zhang, X. R.; Huang, J. B.; Mao, M.; Tang, S. H.; Zhu, B. Y., “From precipitation to vesicles: a study on self-organized assemblies by alkylammonium and its mixtures in polar solvent,” Colloid Polym. Sci. 2001, 279, 1245.

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程學系碩士論文, 2002.

林冠豪, 未發表的研究成果, 國立成功大學化學工程學系, 2003.