本研究以單碳鏈陽離子型界面活性劑 dodecyltrimethylammonium bromide (DTMAB)與雙碳鏈陰離子型界面活性劑dihexadecyl phosphate (DHDP)，經由離子交換法合成類三碳鏈離子對雙親分子dodecyltrimethylammonium-dihexadecyl phosphate (DTMA:DHDP)，利用強制型製程製備出帶負電之陰陽離子液胞並添加順/反-9-十六碳烯酸作為帶電添加劑與膜內穩定劑，以調控液胞的雙層膜結構與物理特性。粒徑與界面電位分析顯示，添加順/反-9-十六碳烯酸的液胞粒徑皆有所增加，脂肪酸不僅能增強液胞表面電性，也可提升液胞穩定性。藉由傅立葉轉換紅外光譜法分析液胞中整體分子碳鏈的自由度，結果顯示順-9-十六碳烯酸因其彎曲結構提升膜流動性，而反-9-十六碳烯酸增強了碳鏈間的凡德瓦作用，使雙層膜分子排列更緊密，並提升液胞雙層膜之相轉移溫度至42 °C。在藥物包覆與釋放行為方面，順-9-十六碳烯酸因較高的膜流動性而提高脂溶性藥物槲皮素的包覆效率以及在pH 6.6酸性環境下的藥物釋放率，反-9-十六碳烯酸則可於pH 7.4類生理環境下因脂肪酸解離產生膜缺陷，加速藥物滲出。而溶血與細胞存活實驗結果顯示，添加脂肪酸能顯著地降低液胞對紅血球與正常/癌細胞之細胞毒性，提升液胞的生物相容性。

In this study, a pseudo-triple chain ion pair amphiphile, dodecyltrimethlyammonium-dihexadecyl phosphate (DTMA:DHDP), was used as the raw material with cis-9-hexadecenoic acid or trans-9-hexadecenoic acid as an additive to fabricate catanionic vesicles by a forced formation process. Through the self-dissociation of fatty acids and their molecular structures, the characteristics of the bilayer structures could be adjusted and could be discussed the effect between cis-trans isomerism of unsaturated fatty acids. Roles of adding unsaturated fatty acids in the modulation of the catanionic vesicle properties were then investigated by the vesicle size, zeta potential, physical stability, and vesicular bilayer fluidity. Thermo-responsive experiments were carried out by increasing temperature of the vesicle dispersions to evaluate the phase transition temperatures and molecular packing changes of the vesicular bilayer structures, thereby further influencing their encapsulation and release behavior. Hemolysis and cytotoxicity assays were adopted to assess the potential application of the vesicles as drug carriers.
In aqueous phase, DTMA:DHDP could form vesicles by a forced formation process. Vesicles are negatively charged because of the preferential dissolution of DTMA+ moieties from the bilayer structures. One could estimate the effect of adding fatty acids on the vesicles size and zeta potential by analyzing by dynamic light scattering analyzer. The results show that the addition of trans-9-hexadecenoic acid increased vesicle size more significantly than cis-9-hexadecenoic, due to stronger van der Waals interactions and the formation of more ordered bilayer structures. When a higher ratio of fatty acids was added, the surface electrical properties of the vesicles would be promoted because of self-dissociated fatty acids. Because of the similar pKa of cis-/trans-9-hexadecenoic acid, the dissociation concentrations of them are similar under the same composition, causing similar effect on zeta potential of vesicles. Thus, vesicles containing either cis- or trans-9-hexadecenoic acid remained stable for months, demonstrating that fatty acids act both as charged additives and bilayer stabilizers.
The influence on the molecular arrangement in the bilayer fluidity and phase transition behavior was modulated by cis-9-hexadecenoic acid or trans-9-hexadecenoic acid. Compared with two kinds of fatty acids, the results revealed that cis-9-hexadecenoic acid increased bilayer fluidity and decreased the phase transition temperature. In contrast, the trans isomer showed the opposite trend, due to the carboxyl group of the fatty acids formed hydrogen bonds with the phosphate groups of DHDP, promoting tighter headgroup packing and reducing the spacing between hydrocarbon chains. Moreover, the addition of 20–30 mol% trans-9-hexadecenoic acid could increase the phase transition temperature of the bilayer structures to 42-43 °C, reaching the application range of drug carriers for temperature-sensitive mild heat therapy.
For the encapsulation and release behaviors, the results showed that cis-9-hexadecenoic acid have the highest encapsulation efficiency with 0.2 mM quercetin. And the overall drug release at pH 6.6 was higher than that at pH 7.4, revealing that the potential of unsaturated fatty acids for pH-responsive drug carrier and cancer therapy applications. The results of biocompatibility showed that the toxicity of the vesicles dispersion to blood cells tended to decrease with the vesicle concentration dilution, and the hemolysis ratio decreased with the increase of the molar ratio of the fatty acids. Compared with cis-9-hexadecenoic acid, the vesicles added with trans-9-hexadecenoic acid could weaken the toxicity to red blood cells because of the rigid bilayer structure. Cell viability experiments showed that the addition of unsaturated fatty acids increased the cell viability of both H1299 (human non-small cell lung cancer cell line) and OUS-11 (human lung normal tissue cell line). Furthermore, the vesicles encapsulated quercetin might further improve biocompatibility by reducing oxidative stress, demonstrating that the biocompatibility could be enhanced by adding fatty acids to form the DTMA:DHDP/unsaturated fatty acid vesicles.

Abdelrazzak, A. B., Hezma, A. M., & El-Bahy, G. S. (2021). ATR-FTIR spectroscopy probing of structural alterations in the cellular membrane of abscopal liver cells. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1863(11), 183726.
Ahmad, N., Banala, V.T., Kushwaha, P., Karvande, A., Sharma, S., Tripathi, A.K., Verma, A., Trivedi, R., and Mishra, P.R. (2016). Quercetin-loaded solid lipid nanoparticles improve osteoprotective activity in an ovariectomized rat model: a preventive strategy for post-menopausal osteoporosis. RSC Advances 6, 97613-97628.
Aiello, C., Andreozzi, P., La Mesa, C., and Risuleo, G. (2010). Biological activity of SDS-CTAB cat-anionic vesicles in cultured cells and assessment of their cytotoxicity ending in apoptosis. Colloids and Surfaces B: Biointerfaces 78, 149-154.
Aleskndrany, A., and Sahin, I. (2020). The effects of Levothyroxine on the structure and dynamics of DPPC liposome: FTIR and DSC studies. Biochimica et Biophysica Acta (BBA)-Biomembranes 1862, 183245.
Alexandre, H., Mathieu, B., and Charpentier, C. (1996). Alteration in membrane fluidity and lipid composition, and modulation of H+-ATPase activity in Saccharomyces cerevisiae caused by decanoic acid. Microbiology 142, 469-475.
Amin, K., and Dannenfelser, R.M. (2006). In vitro hemolysis: guidance for the pharmaceutical scientist. Journal of Pharmaceutical Sciences 95, 1173-1176.
Amrein, A., Hollenstein, H., Quack, M., Zenobi, R., Segall, J., and Zare, R. (1989). Fermi resonance structure in the CH vibrational overtones of CD3CHO. The Journal of Chemical Physics 90, 3944-3951.
Aramaki, Y., Takano, S., and Tsuchiya, S. (1999). Induction of apoptosis in macrophages by cationic liposomes. FEBS Letters 460, 472-476.
Bandyopadhyay, P. (2007). Fatty alcohols or fatty acids as niosomal hybrid carrier: effect on vesicle size, encapsulation efficiency and in vitro dye release. Colloids and Surfaces B: Biointerfaces 58, 68-71.
Bhardwaj, U., and Burgess, D.J. (2010). Physicochemical properties of extruded and non-extruded liposomes containing the hydrophobic drug dexamethasone. International Journal of Pharmaceutics 388, 181-189.
Bhattacharya, S., De, S., and Subramanian, M. (1998). Synthesis and vesicle formation from hybrid bolaphile/amphiphile ion-pairs. Evidence of membrane property modulation by molecular design. The Journal of Organic Chemistry 63, 7640-7651.
Bhattacharya, S., and Haldar, S. (2000). Interactions between cholesterol and lipids in bilayer membranes. Role of lipid headgroup and hydrocarbon chain–backbone linkage. Biochimica et Biophysica Acta (BBA)-Biomembranes 1467, 39-53.
Bitounis, D., Fanciullino, R., Iliadis, A., and Ciccolini, J. (2012). Optimizing druggability through liposomal formulations: new approaches to an old concept. International Scholarly Research Notices 2012, 738432.
Blandamer, M.J., Briggs, B., Cullis, P.M., Rawlings, B.J., and Engberts, J.B. (2003). Vesicle-cholesterol interactions: Effects of added cholesterol on gel-to-liquid crystal transitions in a phospholipid membrane and five dialkyl-based vesicles as monitored using DSC. Physical Chemistry Chemical Physics 5, 5309-5312.
Blanzat, M., Perez, E., Rico-Lattes, I., and Lattes, A. (1999a). Synthesis and anti-HIV activity of catanionic analogs of galactosylceramide. New Journal of Chemistry 23, 1063-1065.
Blanzat, M., Perez, E., Rico-Lattes, I., Prome, D., Prome, J., and Lattes, A. (1999b). New catanionic glycolipids. 1. Synthesis, characterization, and biological activity of double-chain and gemini catanionic analogues of galactosylceramide (galβ1cer). Langmuir 15, 6163-6169.
Boots, A.W., Haenen, G.R., and Bast, A. (2008). Health effects of quercetin: from antioxidant to nutraceutical. European Journal of Pharmacology 585, 325-337.
Bothun, G.D., Boltz, L., Kurniawan, Y., and Scholz, C. (2016). Cooperative effects of fatty acids and n-butanol on lipid membrane phase behavior. Colloids and Surfaces B: Biointerfaces 139, 62-67.
Bouarab, L., Maherani, B., Kheirolomoom, A., Hasan, M., Aliakbarian, B., Linder, M., and Arab-Tehrany, E. (2014). Influence of lecithin–lipid composition on physico-chemical properties of nanoliposomes loaded with a hydrophobic molecule. Colloids and Surfaces B: Biointerfaces 115, 197-204.
Bui, T.T., Suga, K., and Umakoshi, H. (2016). Roles of sterol derivatives in regulating the properties of phospholipid bilayer systems. Langmuir 32, 6176-6184.
Cadena, P.G., Pereira, M.A., Cordeiro, R.B., Cavalcanti, I.M., Neto, B.B., Pimentel, M.d.C.C., Lima Filho, J.L., Silva, V.L., and Santos-Magalhães, N.S. (2013). Nanoencapsulation of quercetin and resveratrol into elastic liposomes. Biochimica et Biophysica Acta (BBA)-Biomembranes 1828, 309-316.
Campbell, R.B., Balasubramanian, S.V., and Straubinger, R.M. (2001). Phospholipid-cationic lipid interactions: influences on membrane and vesicle properties. Biochimica et Biophysica Acta (BBA)-Biomembranes 1512, 27-39.
Carrion, F., De La Maza, A., and Parra, J. (1994). The influence of ionic strength and lipid bilayer charge on the stability of liposomes. Journal of Colloid and Interface Science 164, 78-87.
Casal, H.L., and Mantsch, H.H. (1984). Polymorphic phase behaviour of phospholipid membranes studied by infrared spectroscopy. Biochimica et Biophysica Acta (BBA)-Reviews on Biomembranes 779, 381-401.
Cevher, E., Sezer, A.D., and Çağlar, E. (2012). Gene delivery systems: Recent progress in viral and non-viral therapy. Recent Advances in Novel Drug Carrier Systems 31, 437-470.
Chang, W.-H., Chuang, Y.-T., Yu, C.-Y., Chang, C.-H., and Yang, Y.-M. (2017). Effects of sterol-like additives on phase transition behavior of ion-pair amphiphile bilayers. Journal of Oleo Science 66, 1229-1238.
Chester, D.W., Tourtellotte, M.E., Melchior, D.L., and Romano, A.H. (1986). The influence of saturated fatty acid modulation of bilayer physical state on cellular and membrane structure and function. Biochimica et Biophysica Acta (BBA)-Biomembranes 860, 383-398.
Choi, S., Kang, B., Yang, E., Kim, K., Kwak, M.K., Chang, P.-S., and Jung, H.-S. (2023). Precise control of liposome size using characteristic time depends on solvent type and membrane properties. Scientific Reports 13, 4728.
Chung, M.-H., and Chung, Y.-C. (2002). Polymerized ion pair amphiphile that shows remarkable enhancement in encapsulation efficiency and very slow release of fluorescent markers. Colloids and Surfaces B: Biointerfaces 24, 111-121.
Chung, M.-H., Park, C., Chun, B.C., and Chung, Y.-C. (2004). Polymerized ion pair amphiphile vesicles with pH-sensitive transformation and controlled release property. Colloids and Surfaces B: Biointerfaces 34, 179-184.
Chung, M.-H., Park, M.-J., Chun, B.C., and Chung, Y.-C. (2003). Encapsulation and permeation properties of the polymerized ion pair amphiphile vesicle that has an additional carboxyl group on anionic chain. Colloids and Surfaces B: Biointerfaces 28, 83-93.
Chung, Y.C., and Regen, S.L. (1993). Counterion control over the barrier properties of bilayers derived from double-chain ionic surfactants. Langmuir 9, 1937-1939.
Cistola, D.P., Hamilton, J.A., Jackson, D., and Small, D.M. (1988). Ionization and phase behavior of fatty acids in water: application of the Gibbs phase rule. Biochemistry 27, 1881-1888.
Comalada, M., Camuesco, D., Sierra, S., Ballester, I., Xaus, J., Gálvez, J., and Zarzuelo, A. (2005). In vivo quercitrin anti‐inflammatory effect involves release of quercetin, which inhibits inflammation through down‐regulation of the NF‐κB pathway. European Journal of Immunology 35, 584-592.
Cortesi, R., Esposito, E., Menegatti, E., Gambari, R., and Nastruzzi, C. (1996). Effect of cationic liposome composition on in vitro cytotoxicity and protective effect on carried DNA. International Journal of Pharmaceutics 139, 69-78.
Crosasso, P., Ceruti, M., Brusa, P., Arpicco, S., Dosio, F., and Cattel, L. (2000). Preparation, characterization and properties of sterically stabilized paclitaxel-containing liposomes. Journal of Controlled Release 63, 19-30.
Demirbolat, G.M., Erdoğan, Ö., Coşkun, G.P., and Çevik, Ö. (2022). PEG4000 modified liposomes enhance the solubility of quercetin and improve the liposome functionality: in vitro characterization and the cellular efficacy. Turkish Journal of Chemistry 46, 1011-1023.
Denison, M.S., and Nagy, S.R. (2003). Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals. Annual Review of Pharmacology and Toxicology 43, 309-334.
Denison, M.S., Pandini, A., Nagy, S.R., Baldwin, E.P., and Bonati, L. (2002). Ligand binding and activation of the Ah receptor. Chemico-Biological Interactions 141, 3-24.
Devaraj, G.N., Parakh, S., Devraj, R., Apte, S., Rao, B.R., and Rambhau, D. (2002). Release studies on niosomes containing fatty alcohols as bilayer stabilizers instead of cholesterol. Journal of Colloid and Interface Science 251, 360-365.
Dhawan, V.V., and Nagarsenker, M.S. (2017). Catanionic systems in nanotherapeutics–Biophysical aspects and novel trends in drug delivery applications. Journal of Controlled Release 266, 331-345.
Di, J., Gao, X., Du, Y., Zhang, H., Gao, J., and Zheng, A. (2021). Size, shape, charge and “stealthy” surface: Carrier properties affect the drug circulation time in vivo. Asian Journal of Pharmaceutical Sciences 16, 444-458.
Douliez, J.-P., Houssou, B.H., Fameau, A.-L., Navailles, L., Nallet, F., Grélard, A., Dufourc, E.J., and Gaillard, C. (2016). Self-assembly of bilayer vesicles made of saturated long chain fatty acids. Langmuir 32, 401-410.
Duraj, J., Zazrivcova, K., Bodo, J., Sulikova, M., and Sedlak, J. (2005). Flavonoid quercetin, but not apigenin or luteolin, induced apoptosis in human myeloid leukemia cells and their resistant variants. Neoplasma 52, 273-279.
Eastman, S., Siegel, C., Tousignant, J., Smith, A., Cheng, S., and Scheule, R. (1997). Biophysical characterization of cationic lipid: DNA complexes. Biochimica et Biophysica Acta (BBA)-Biomembranes 1325, 41-62.
Egert, S., Bosy-Westphal, A., Seiberl, J., Kürbitz, C., Settler, U., Plachta-Danielzik, S., Wagner, A.E., Frank, J., Schrezenmeir, J., and Rimbach, G. (2009). Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a double-blinded, placebo-controlled cross-over study. British Journal of Nutrition 102, 1065-1074.
Farkuh, L., Hennies, P.T., Nunes, C., Reis, S., Barreiros, L., Segundo, M.A., Oseliero Filho, P.L., Oliveira, C.L., Cassago, A., and Portugal, R.V. (2019). Characterization of phospholipid vesicles containing lauric acid: physicochemical basis for process and product development. Heliyon 5.
Feitosa, E., Alves, F.R., Niemiec, A., Real Oliveira, M.E.C., Castanheira, E.M., and Baptista, A.L. (2006). Cationic liposomes in mixed didodecyldimethylammonium bromide and dioctadecyldimethylammonium bromide aqueous dispersions studied by differential scanning calorimetry, Nile Red fluorescence, and turbidity. Langmuir 22, 3579-3585.
Fischer, A., Hebrant, M., and Tondre, C. (2002). Glucose encapsulation in catanionic vesicles and kinetic study of the entrapment/release processes in the sodium dodecyl benzene sulfonate/cetyltrimethylammonium tosylate/water system. Journal of Colloid and Interface Science 248, 163-168.
Franzé, S., Selmin, F., Samaritani, E., Minghetti, P., and Cilurzo, F. (2018). Lyophilization of liposomal formulations: still necessary, still challenging. Pharmaceutics 10, 139.
Fukuda, H., Kawata, K., Okuda, H., and Regen, S.L. (1990). Bilayer-forming ion pair amphiphiles from single-chain surfactants. Journal of the American Chemical Society 112, 1635-1637.
Garg, T., and K Goyal, A. (2014). Liposomes: targeted and controlled delivery system. Drug Delivery Letters 4, 62-71.
Gebicki, J., and Hicks, M. (1973). Ufasomes are stable particles surrounded by unsaturated fatty acid membranes. Nature 243, 232-234.
Granado-Serrano, A.B., Martiín, M.A., Bravo, L., Goya, L., and Ramos, S. (2006). Quercetin induces apoptosis via caspase activation, regulation of Bcl-2, and inhibition of PI-3-kinase/Akt and ERK pathways in a human hepatoma cell line (HepG2). The Journal of Nutrition 136, 2715-2721.
Guha, P., Roy, B., Karmakar, G., Nahak, P., Koirala, S., Sapkota, M., Misono, T., Torigoe, K., and Panda, A.K. (2015). Ion-pair amphiphile: a neoteric substitute that modulates the physicochemical properties of biomimetic membranes. The Journal of Physical Chemistry B 119, 4251-4262.
Guo, L., and Santschi, P.H. (2007). Ultrafiltration and its applications to sampling and characterisation of aquatic colloids. IUPAC Series on Analytical and Physical Chemistry of Environmental Systems 10, 159.
Hargreaves, W.R., and Deamer, D.W. (1978). Liposomes from ionic, single-chain amphiphiles. Biochemistry 17, 3759-3768.
Heimburg, T. (2000). A model for the lipid pretransition: coupling of ripple formation with the chain-melting transition. Biophysical Journal 78, 1154-1165.
Hirano, K., Fukuda, H., and Regen, S.L. (1991). Polymerizable ion-paired amphiphiles. Langmuir 7, 1045-1047.
Hong, S.-S., Kim, S.H., and Lim, S.-J. (2015). Effects of triglycerides on the hydrophobic drug loading capacity of saturated phosphatidylcholine-based liposomes. International Journal of Pharmaceutics 483, 142-150.
Huang, A., Huang, L., and Kennel, S.J. (1980). Monoclonal antibody covalently coupled with fatty acid. A reagent for in vitro liposome targeting. Journal of Biological Chemistry 255, 8015-8018.
Ibarguren, M., López, D.J., and Escribá, P.V. (2014). The effect of natural and synthetic fatty acids on membrane structure, microdomain organization, cellular functions and human health. Biochimica et Biophysica Acta (BBA)-Biomembranes 1838, 1518-1528.
Immordino, M.L., Brusa, P., Arpicco, S., Stella, B., Dosio, F., and Cattel, L. (2003). Preparation, characterization, cytotoxicity and pharmacokinetics of liposomes containing docetaxel. Journal of Controlled Release 91, 417-429.
Israelachvili, J.N., Mitchell, D.J., and Ninham, B.W. (1976). Theory of self-assembly of hydrocarbon amphiphiles into micelles and bilayers. Journal of the Chemical Society, Faraday Transactions 2: Molecular and Chemical Physics 72, 1525-1568.
Jenski, L.J., Zerouga, M., and Stillwell, W. (1995). ω-3 Fatty acid–containing liposomes in cancer therapy. Proceedings of the Society for Experimental Biology and Medicine 210, 227-233.
Jubeh, T.T., Barenholz, Y., and Rubinstein, A. (2004). Differential adhesion of normal and inflamed rat colonic mucosa by charged liposomes. Pharmaceutical Research 21, 447-453.
Jurašin, D.D., Šegota, S., Čadež, V., Selmani, A., and Sikirć, M.D. (2017). Recent advances in catanionic mixtures. Application and Characterization of Surfactants 1, 33-73.
Kaler, E.W., Murthy, A.K., Rodriguez, B.E., and Zasadzinski, J.A. (1989). Spontaneous vesicle formation in aqueous mixtures of single-tailed surfactants. Science 245, 1371-1374.
Kaliannan, K., Wang, B., Li, X.-Y., Kim, K.-J., and Kang, J.X. (2015). A host-microbiome interaction mediates the opposing effects of omega-6 and omega-3 fatty acids on metabolic endotoxemia. Scientific Reports 5, 11276.
Keough, K., and Davis, P. (1979). Gel to liquid-crystalline phase transitions in water dispersions of saturated mixed-acid phosphatidylcholines. Biochemistry 18, 1453-1459.
Kim, S., Oh, W.-K., Jeong, Y.S., Hong, J.-Y., Cho, B.-R., Hahn, J.-S., and Jang, J. (2011). Cytotoxicity of, and innate immune response to, size-controlled polypyrrole nanoparticles in mammalian cells. Biomaterials 32, 2342-2350.
Kim, W.K., Bang, M.H., Kim, E.S., Kang, N.E., Jung, K.C., Cho, H.J., and Park, J.H. (2005). Quercetin decreases the expression of ErbB2 and ErbB3 proteins in HT-29 human colon cancer cells. The Journal of Nutritional Biochemistry 16, 155-162.
Knothe, G., and Dunn, R.O. (2009). A comprehensive evaluation of the melting points of fatty acids and esters determined by differential scanning calorimetry. Journal of the American Oil Chemists' Society 86, 843-856.
Kondo, Y., Uchiyama, H., Yoshino, N., Nishiyama, K., and Abe, M. (1995). Spontaneous vesicle formation from aqueous solutions of didodecyldimethylammonium bromide and sodium dodecyl sulfate mixtures. Langmuir 11, 2380-2384.
Kranenburg, M., and Smit, B. (2005). Phase behavior of model lipid bilayers. The Journal of Physical Chemistry B 109, 6553-6563.
Kumari, A., Yadav, S.K., Pakade, Y.B., Singh, B., and Yadav, S.C. (2010). Development of biodegradable nanoparticles for delivery of quercetin. Colloids and Surfaces B: Biointerfaces 80, 184-192.
Kuo, A.-T., and Chang, C.-H. (2016). Recent strategies in the development of catanionic vesicles. Journal of Oleo Science 65, 377-384.
Large, D.E., Abdelmessih, R.G., Fink, E.A., and Auguste, D.T. (2021). Liposome composition in drug delivery design, synthesis, characterization, and clinical application. Advanced Drug Delivery Reviews 176, 113851.
Lasic, D.D. (1993). Liposomes: from physics to applications. Elsevier. 575.
Lasic, D.D., and Papahadjopoulos, D. (1996). Liposomes and biopolymers in drug and gene delivery. Current Opinion in Solid State and Materials Science 1, 392-400.
Lee, J., Chi, G.-Y., and Lim, J. (2017). Effect of fatty acid on the membrane fluidity of liposomes. Applied Chemistry for Engineering 28, 177-185.
Lee, M. K. (2020). Liposomes for enhanced bioavailability of water-insoluble drugs: In vivo evidence and recent approaches. Pharmaceutics, 12(3), 264.
Leekumjorn, S., Cho, H.J., Wu, Y., Wright, N.T., Sum, A.K., and Chan, C. (2009). The role of fatty acid unsaturation in minimizing biophysical changes on the structure and local effects of bilayer membranes. Biochimica et Biophysica Acta (BBA)-Biomembranes 1788, 1508-1516.
Lewis, R.N., and McElhaney, R.N. (2013). Membrane lipid phase transitions and phase organization studied by Fourier transform infrared spectroscopy. Biochimica et Biophysica Acta (BBA)-Biomembranes 1828, 2347-2358.
Liu, Y.-S., Wen, C.-F., and Yang, Y.-M. (2012). Development of ethosome-like catanionic vesicles for dermal drug delivery. Journal of the Taiwan Institute of Chemical Engineers 43, 830-838.
Maulucci, G., Cohen, O., Daniel, B., Sansone, A., Petropoulou, P., Filou, S., Spyridonidis, A., Pani, G., De Spirito, M., and Chatgilialoglu, C. (2016). Fatty acid-related modulations of membrane fluidity in cells: detection and implications. Free Radical Research 50, S40-S50.
Morini, M.A., Minardi, R.M., Schulz, P.C., Puig, J.E., and Hernández-Vargas, M.E. (1995). Basicity of dodecyltrimethylammonium hydroxide. Colloids and Surfaces A: Physicochemical and Engineering Aspects 103, 37-40.
Murakami, A., Ashida, H., and Terao, J. (2008). Multitargeted cancer prevention by quercetin. Cancer Letters 269, 315-325.
Muranushi, N., Takagi, N., Muranishi, S., and Sezaki, H. (1981). Effect of fatty acids and monoglycerides on permeability of lipid bilayer. Chemistry and Physics of Lipids 28, 269-279.
Namani, T., Ishikawa, T., Morigaki, K., and Walde, P. (2007). Vesicles from docosahexaenoic acid. Colloids and Surfaces B: Biointerfaces 54, 118-123.
New, R.R. (1990). Liposomes. IRL at Oxford University Press. 291.
Nolan, C.J., Madiraju, M.S., Delghingaro-Augusto, V., Peyot, M.-L., and Prentki, M. (2006). Fatty acid signaling in the β-cell and insulin secretion. Diabetes 55, S16-S23.
Nolan, C. J., & Larter, C. Z. (2009). Lipotoxicity: why do saturated fatty acids cause and monounsaturates protect against it?. Journal of Gastroenterology and Hepatology, 24(5), 703-706.
Oberhauser, L., Granziera, S., Colom, A., Goujon, A., Lavallard, V., Matile, S., Roux, A., Brun, T., and Maechler, P. (2020). Palmitate and oleate modify membrane fluidity and kinase activities of INS-1E β-cells alongside altered metabolism-secretion coupling. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research 1867, 118619.
Omodeo-Sale, M.F., Palestini, P., and Masserini, M. (1992). Thermotropic behavior of fatty acid ethyl esters in phospholipid liposomes. Chemistry and Physics of Lipids 61, 149-155.
Papahadjopoulos, D., Jacobson, K., Nir, S., and Isac, I. (1973). Phase transitions in phospholipid vesicles Fluorescence polarization and permeability measurements concerning the effect of temperature and cholesterol. Biochimica et Biophysica Acta (BBA)-Biomembranes 311, 330-348.
Park, S.N., Lee, M.H., Kim, S.J., and Yu, E.R. (2013). Preparation of quercetin and rutin-loaded ceramide liposomes and drug-releasing effect in liposome-in-hydrogel complex system. Biochemical and Biophysical Research Communications 435, 361-366.
Patel, V.R., and Agrawal, Y. (2011). Nanosuspension: An approach to enhance solubility of drugs. Journal of Advanced Pharmaceutical Technology & Research 2, 81-87.
Peng, B., Ding, X. Y., Sun, C., Yang, Y. N., Gao, Y. J., & Zhao, X. (2017). The chain order of binary unsaturated lipid bilayers modulated by aromatic-residue-containing peptides: an ATR-FTIR spectroscopy study. RSC Advances, 7(47), 29386-29394.
Poorsargol, M., Rahdar, A., Baino, F., and Karimi, P. (2023). Theoretical studies on the quercetin interactions in the oil-in-water F127 microemulsion: A DFT and MD investigation. Journal of Molecular Liquids 383, 122037.
Pralhad, T., and Rajendrakumar, K. (2004). Study of freeze-dried quercetin–cyclodextrin binary systems by DSC, FT-IR, X-ray diffraction and SEM analysis. Journal of Pharmaceutical and Biomedical Analysis 34, 333-339.
Prentki, M., Corkey, B.E., and Madiraju, S.M. (2020). Lipid-associated metabolic signalling networks in pancreatic beta cell function. Diabetologia 63, 10-20.
Priyadarsini, R.V., Murugan, R.S., Maitreyi, S., Ramalingam, K., Karunagaran, D., and Nagini, S. (2010). The flavonoid quercetin induces cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells through p53 induction and NF-κB inhibition. European Journal of Pharmacology 649, 84-91.
Psahoulia, F.H., Drosopoulos, K.G., Doubravska, L., Andera, L., and Pintzas, A. (2007). Quercetin enhances TRAIL-mediated apoptosis in colon cancer cells by inducing the accumulation of death receptors in lipid rafts. Molecular Cancer Therapeutics 6, 2591-2599.
Pucci, C., Scipioni, A., Diociaiuti, M., La Mesa, C., Pérez, L., and Pons, R. (2015). Catanionic vesicles and DNA complexes: a strategy towards novel gene delivery systems. RSC Advances 5, 81168-81175.
Ratnam, D.V., Ankola, D.D., Bhardwaj, V., Sahana, D.K., and Kumar, M.R. (2006). Role of antioxidants in prophylaxis and therapy: A pharmaceutical perspective. Journal of Controlled Release 113, 189-207.
Rustan, A.C., and Drevon, C.A. (2005). Fatty acids: structures and properties. Encyclopedia of Life Sciences 1, 1-7.
Šegota, S., Težak, Đ., and Talmon, Y. (2005). New catanionic mixtures of didodecyldimethylammonium bromide/sodium dodecylbenzene sulfonate/water with special reference to spontaneous formation of vesicles. II. Size and shape analysis by SAXS, light scattering, cryo‐TEM, and light microscopy. Soft Materials 3, 51-69.
Sengupta, A., Ghosh, S., and Das, S. (2001). Modulation of DMBA induced genotoxicity in bone marrow by quercetin during skin carcinogenesis. Journal of Experimental & Clinical Cancer Research: CR 20, 131-134.
Shen, J., Wang, Y., Fan, P., Jiang, L., Zhuang, W., Han, Y., and Zhang, H. (2019). Self-assembled vesicles formed by C18 unsaturated fatty acids and sodium dodecyl sulfate as a drug delivery system. Colloids and Surfaces A: Physicochemical and Engineering Aspects 568, 66-74.
Shome, A., Kar, T., and Das, P.K. (2011). Spontaneous Formation of Biocompatible Vesicles in Aqueous Mixtures of Amino Acid‐Based Cationic Surfactants and SDS/SDBS. ChemPhysChem 12, 369-378.
Smith, R., and Tanford, C. (1972). The critical micelle concentration of l-α-dipalmitoylphosphatidylcholine in water and water/methanol solutions. Journal of Molecular Biology 67, 75-83.
Soussan, E., Cassel, S., Blanzat, M., and Rico‐Lattes, I. (2009). Drug delivery by soft matter: matrix and vesicular carriers. Angewandte Chemie International Edition 48, 274-288.
Subedi, R.K., Oh, S.Y., Chun, M.K., and Choi, H.K. (2010). Recent advances in transdermal drug delivery. Archives of Pharmacal Research 33, 339-351.
Sumida, Y., Masuyama, A., Takasu, M., Kida, T., Nakatsuji, Y., Ikeda, I., and Nojima, M. (2000). Behavior of self-organized molecular assemblies composed of phosphatidylcholines and synthetic triple-chain amphiphiles in water. Langmuir 16, 8005-8009.
Sumida, Y., Masuyama, A., Takasu, M., Kida, T., Nakatsuji, Y., Ikeda, I., and Nojima, M. (2001). New pH-Sensitive Vesicles. Release control of trapped materials from the inner aqueous phase of vesicles made from triple-chain amphiphiles bearing two carboxylate groups. Langmuir 17, 609-612.
Teixeira, C., Blanzat, M., Koetz, J., Rico-Lattes, I., and Brezesinski, G. (2006). In-plane miscibility and mixed bilayer microstructure in mixtures of catanionic glycolipids and zwitterionic phospholipids. Biochimica et Biophysica Acta (BBA)-Biomembranes 1758, 1797-1808.
Tomašić, V., Štefanić, I., and Filipović-Vinceković, N. (1999). Adsorption, association and precipitation in hexadecyltrimethylammonium bromide/sodium dodecyl sulfate mixtures. Colloid and Polymer Science 277, 153-163.
Tyler, A.I., Greenfield, J.L., Seddon, J.M., Brooks, N.J., and Purushothaman, S. (2019). Coupling phase behavior of fatty acid containing membranes to membrane bio-mechanics. Frontiers in Cell and Developmental Biology 7, 187.
Vautrin, C., Zemb, T., Schneider, M., and Tanaka, M. (2004). Balance of pH and ionic strength influences on chain melting transition in catanionic vesicles. The Journal of Physical Chemistry B 108, 7986-7991.
Vist, M.R., and Davis, J.H. (1990). Phase equilibria of cholesterol/dipalmitoylphosphatidylcholine mixtures: deuterium nuclear magnetic resonance and differential scanning calorimetry. Biochemistry 29, 451-464.
Vlachy, N., Touraud, D., Heilmann, J., and Kunz, W. (2009). Determining the cytotoxicity of catanionic surfactant mixtures on HeLa cells. Colloids and Surfaces B: Biointerfaces 70, 278-280.
Voinea, M., and Simionescu, M. (2002). Designing of ‘intelligent’liposomes for efficient delivery of drugs. Journal of Cellular and Molecular Medicine 6, 465-474.
Volate, S.R., Davenport, D.M., Muga, S.J., and Wargovich, M.J. (2005). Modulation of aberrant crypt foci and apoptosis by dietary herbal supplements (quercetin, curcumin, silymarin, ginseng and rutin). Carcinogenesis 26, 1450-1456.
Walde, P., Namani, T., Morigaki, K., and Hauser, H. (2007). Formation and properties of fatty acid vesicles (liposomes). Liposome Technology 1, 1-19.
Wang, C., Tang, S., Huang, J., Zhang, X., and Fu, H. (2002). Transformation from precipitates to vesicles in mixed cationic and anionic surfactant systems. Colloid and Polymer Science 280, 770-774.
Wang, J., and Li, Y. (2019). CD36 tango in cancer: signaling pathways and functions. Theranostics 9, 4893.
Xiang, M.S., Tan, J.K., and Macia, L. (2019). Fatty acids, gut bacteria, and immune cell function. The Molecular Nutrition of Fats, 151-164.
Xu, W., Wang, X., Zhong, Z., Song, A., and Hao, J. (2013). Influence of counterions on lauric acid vesicles and theoretical consideration of vesicle stability. The Journal of Physical Chemistry B 117, 242-251.
Yokouchi, Y., Tsunoda, T., Imura, T., Yamauchi, H., Yokoyama, S., Sakai, H., and Abe, M. (2001). Effect of adsorption of bovine serum albumin on liposomal membrane characteristics. Colloids and Surfaces B: Biointerfaces 20, 95-103.
Yokoyama, S., Inagaki, A., Imura, T., Ohkubo, T., Tsubaki, N., Sakai, H., and Abe, M. (2005). Membrane properties of cationic liposomes composed of dipalmitoylphosphatidylcholine and dipalmityldimethylammonium bromide. Colloids and Surfaces B: Biointerfaces 44, 204-210.
Yu, W.-Y., Yang, Y.-M., and Chang, C.-H. (2005). Cosolvent effects on the spontaneous formation of vesicles from 1:1 anionic and cationic surfactant mixtures. Langmuir 21, 6185-6193.
Zalba, S., Ten Hagen, T.L., Burgui, C., and Garrido, M.J. (2022). Stealth nanoparticles in oncology: Facing the PEG dilemma. Journal of Controlled Release 351, 22-36.
呂奇達. (2005). 帶正電的陰陽離子液胞與 DNA 之結合行為的探討. 成功大學化學工程學系學位論文, 1-110.
林冠豪. (2004). 帶電的陰陽離子液胞之製備及物理穩定性研究. 成功大學化學工程學系學位論文, 1-86.
李威達. (2008). 陰陽離子型液胞組成材料之混合單分子層中分子作用的探討. 成功大學化學工程學系博士論文, 1-185.
李威漢. (2010). 陰陽離子界面活性劑的製備及其相轉移行為的熱卡分析. 成功大學化學工程學系碩士論文, 1-130.
李家如. (2011). 含不對稱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. 成功大學化學工程學系學位論文, 1-88.
李承軒. (2015). 帶正電陰陽離子液胞及其與 DNA 形成之複合物的物理穩定性. 成功大學化學工程學系學位論文, 1-113.
林佳蓉. (2022). 帶負電陰陽離子液胞之溫度敏感特性的調控. 成功大學化學工程學系學位論文, 1-88.
林昇宏. (2024). 帶正電陰陽離子液胞/硫酸軟骨素複合物的特性分析. 成功大學化學工程學系學位論文, 1-96.
黃柏淞. (2020). 由帶正電陰陽離子液胞與玻尿酸製備之複合物的物理性質和包覆行為. 成功大學化學工程學系學位論文, 1-151.
許筱妤. (2024). 碳鏈長度與膽固醇濃度對類三碳鏈離子對雙親分子形成之陰陽離子液胞特性的影響. 成功大學化學工程學系學位論文, 1-102.
張維芬. (2012). 添加劑對雙十六碳鏈離子對雙親分子形成之陰陽離子液胞物化特性的影響. 成功大學化學工程學系學位論文, 1-106.
張家綺. (2016). 以碳鏈長度為16-16-12之三碳鏈離子對雙親分子製備之陰陽離子液胞的物理特性. 成功大學化學工程學系碩士論文, 1-98.
張琇茹. (2023). 利用飽和脂肪酸調控類三碳鏈離子對雙親分子形成之陰陽離子液胞的雙層膜結構有序性及帶電特性. 成功大學化學工程學系學位論文, 1-159.
陳振豪. (2016). 不對稱碳鏈對離子對雙親分子雙層膜結構性質之影響以及環糊精/聚胺酸雙親分子凝膠化機制之探討. 成功大學化學工程學系學位論文, 1-96.
陳怡靜. (2019). 三碳鏈離子對雙親分子/穩定液胞添加劑之混合Langmuir單分子層行為的探討. 成功大學化學工程學系學位論文, 1-106.
蘇于晴. (2016). 具三條十六碳鏈之離子對雙親分子形成的陰陽離子液胞物理性質及液胞雙層膜中分子排列特性：膽固醇效應. 成功大學化學工程學系學位論文, 1-116.
蘇珮萱. (2017). 類三碳鏈離子對雙親分子/膽固醇混合系統形成之陰陽離子液胞的特性分析. 成功大學化學工程學系學位論文, 1-112.
楊婕妤. (2024). 類三碳鏈離子對雙親分子形成之陰陽離子液胞的膽汁酸誘導酸鹼響應特性. 成功大學化學工程學系學位論文, 1-106.
吳芷容. (2008). 利用帶正電的陰陽離子液胞做為 DNA 載體之可行性的研究. 成功大學化學工程學系學位論文, 1-143.
洪振益. (2009). 溫度效應對帶電陰陽離子液胞釋放行為的影響. 成功大學化學工程學系學位論文, 1-144.
王鈺婷. (2015). 帶負電陰陽離子液胞的物化特性及維他命 E 醋酸酯包覆效率-離子對雙親分子碳鏈結構的影響. 成功大學化學工程學系學位論文, 1-117.