油酸在氢氧化胆碱水溶液中的自组装及十二烷基硫酸钠对其囊泡化pH窗口的影响

doi:10.3969/j.issn.2097-2806.2023.09.004

摘要/Abstract

摘要：

脂肪酸囊泡具有封闭双层膜结构，可包埋活性分子。以油酸（OA）为模型脂肪酸，依据pH滴定曲线和目视观察法划分胶束、囊泡、乳液或油水分相等相区，确定了OA在氢氧化胆碱（ChOH）中囊泡化的pH窗口为7.5~9.1，用动态光散射、相差显微镜结合透射电子显微镜技术进一步表征了OA/ChOH囊泡的尺寸和形貌，呈现尺度多分散性。为进一步改善OA/ChOH囊泡形成pH范围窄且远离人体生理条件的缺陷，加入阴离子表面活性剂十二烷基硫酸钠（SDS），结果表明SDS摩尔分数（x）为0.1时即可将囊泡化pH窗口向酸性迁移至生理pH条件附近；随x增加，复合囊泡pH窗口呈现向酸性拓宽的趋势，甚至可达到强酸性条件。复合囊泡形成的主要原因是SDS与OA分子间的氢键作用，在较低pH范围内可代替“酸-皂”二聚体间的氢键作用。复合囊泡作为包埋体时，具有较高的包封率和载药量以及良好的缓释效果。

关键词: 油酸, 氢氧化胆碱, 十二烷基硫酸钠, 脂肪酸囊泡, pH窗口

Abstract:

Fatty acid vesicles have closed bilayer structure and can encapsulate active molecules. Taking oleic acid （OA） as model fatty acid, the phase regions including micelles, vesicles, emulsion and oil-water separation were designated using pH titration curve and visual observation method. The pH window of OA/hydroxide choline （ChOH） vesicles was determined to be 7.5-9.1. The size and morphology of OA/ChOH vesicles were characterized using dynamic light scattering, phase contrast microscopy and transmission electron microscopy, showing size polydispersity. An anionic surfactant, sodium dodecyl sulfate （SDS）, was added to OA/ChOH system, aiming to shift and expand the pH window of OA/ChOH vesicles to a range from being acidic to slightly alkaline, depending on the molar ratio （x） of SDS. At x=0.1, the pH window could be shifted to lower pH which matched the pH range of body fluid. With increasing x, the pH window was significantly broadened towards acidity, even reaching a very low pH of 1.3. The hydrogen bonding between SDS and OA molecules played a key role in the vesicle formation in the lower pH range, which had replaced the hydrogen bonding between acid-soap dimers of fatty acids. The composite vesicles as capsules had higher encapsulation efficiency, drug-loading capacity, and sustained drug release properties. This research work could provide a theoretical guidance for potential application in drug delivery and cosmetics.

Key words: oleic acid, choline hydroxide, sodium dodecyl sulfate, fatty acid vesicle, pH window

中图分类号:

TQ423

梁馨, 胥会芳, 陆松, 李圆圆, 王斯佳, 谢彩侠. 油酸在氢氧化胆碱水溶液中的自组装及十二烷基硫酸钠对其囊泡化pH窗口的影响[J]. 日用化学工业（中英文）, 2023, 53(9): 1018-1028.

Liang Xin, Xu Huifang, Lu Song, Li Yuanyuan, Wang Sijia, Xie Caixia. Self-assembly of oleic acid in aqueous solution of choline hydroxide and effects of sodium dodecyl sulfate on the pH window thereof for vesicle formation[J]. China Surfactant Detergent & Cosmetics, 2023, 53(9): 1018-1028.

图/表 12

图 1

图 2

图 3

表 1

图 4

图 5

图 6

图 7

图 8

图 9

图 10

图 11

参考文献 35

[1]	Gebicki J M, Hicks M. Ufasomes are stable particles surrounded by unsaturated fatty acid membranes[J]. Nature, 1973, 243 (5404) : 232-234. doi: 10.1038/243232a0
[2]	Cistola D P, Hamilton J A, Jackson D, et al. Ionization and phase behavior of fatty acids in water: application of the Gibbs phase rule[J]. Biochemistry, 1988, 27 (6) : 1881-1888. pmid: 3378036
[3]	Martin N, Douliez J P. Fatty acid vesicles and coacervates as model prebiotic protocells[J]. ChemSystemsChem, 2021, 3 (6): e2100024. doi: 10.1002/syst.v3.6
[4]	Namani T, Walde P. From decanoate micelles to decanoic acid/dodecylbenzenesulfonate vesicles[J]. Langmuir, 2005, 21 (14) : 6210-6219. pmid: 15982022
[5]	Shen J, Wang Y, Fan P, et al. Self-assembled vesicles formed by C18 unsaturated fatty acids and sodium dodecyl sulfate as a drug delivery system[J]. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2019, 568: 66-74. doi: 10.1016/j.colsurfa.2019.01.070
[6]	Liu H, Meng X, Li L, et al. Synergistic effect on antioxidant activity of vitamin C provided with acidic vesiculation of hybrid fatty acids[J]. Journal of Functional Foods, 2021, 85: 104647. doi: 10.1016/j.jff.2021.104647
[7]	Guo X, Yang J. Preparation of oleic acid-carboxymethylcellulose sodium composite vesicle and its application in encapsulating nicotinamide[J]. Polymer International, 2021, 70 (11) : 1604-1611. doi: 10.1002/pi.v70.11
[8]	Nistor C L, Ianchis R, Ghiurea M, et al. Aqueous dispersions of silica stabilized with oleic acid obtained by green chemistry[J]. Nanomaterials, 2016, 6 (1): 9. doi: 10.3390/nano6010009
[9]	Renoncourt A, Vlachy N, Bauduin P, et al. Spontaneous vesicle formation of an industrial single-chain surfactant at acidic pH and at room-temperature[J]. ChemPhysChem, 2006, 7 (9) : 1892-1896. pmid: 16881085
[10]	Lee J H, Danino D, Raghavan S R. Polymerizable vesicles based on a single-tailed fatty acid surfactant: a simple route to robust nanocontainers[J]. Langmuir, 2009, 25 (3) : 1566-1571. doi: 10.1021/la802373j
[11]	Fan Y, Fang Y, Ma L, et al. Investigation of micellization and vesiculation of conjugated linoleic acid by means of self-assembling and self-crosslinking[J]. Journal of Surfactants and Detergents, 2015, 18 (1) : 179-188. doi: 10.1007/s11743-014-1591-4
[12]	Liang X, Fan Y, Fang Y, et al. Investigation of vesiculation of conjugated linoleic acid assisted by monolauryl phosphate[J]. Chemical Journal of Chinese Universities-Chinese, 2017, 38 (9) : 1639-1644.
[13]	Ma J, Fan Y, Fang Y. Influence of alkyl polyglucoside on migration and extension of pH window for forming fatty acid vesicles of conjugated linoleic acid[J]. Acta Physico-Chimica Sinica, 2015, 31 (7) : 1359-1364. doi: 10.3866/PKU.WHXB201504131
[14]	Apel C L, Deamer D W, Mautner M N. Self-assembled vesicles of monocarboxylic acids and alcohols: conditions for stability and for the encapsulation of biopolymers[J]. Biochimica et Biophysica Acta (BBA)-Biomembranes, 2002, 1559 (1) : 1-9. doi: 10.1016/S0005-2736(01)00400-X
[15]	Sarkar S, Dagar S, Verma A, et al. Compositional heterogeneity confers selective advantage to model protocellular membranes during the origins of cellular life[J]. Scientific Reports, 2020, 10 (1) :1-11. doi: 10.1038/s41598-019-56847-4
[16]	Li L, Fang Y, Xia Y, et al. Monosaccharides driving the formation of conjugated linoleic acid vesicles in near-neutral solutions via weak noncovalent bonding interactions[J]. Journal of Molecular Liquids, 2022, 351: 118656. doi: 10.1016/j.molliq.2022.118656
[17]	Fan Y, Fan M, Fang Y, et al. Size polydispersity of oleic acid vesicles and effects of diols on the pH window of the vesicles[J]. Chemical Journal of Chinese Universities, 2021, 42 (8) : 2574-2580. doi: 10.7503/cjcu20210053
[18]	Li L, Fang Y, Xia Y, et al. Effects of amine structures on the pH window of oleic acid vesicle[J]. Chemical Journal of Chinese Universities, 2022, 43 (8) : 2574-2580.
[19]	Arnould A, Cousin F, Chabas L, et al. Impact of the molar ratio and the nature of the counter-ion on the self-assembly of myristic acid[J]. Journal of Colloid and Interface Science, 2018, 510: 133-141. doi: S0021-9797(17)31089-5 pmid: 28942163
[20]	Klein R, Kellermeier M, Drechsler M, et al. Solubilisation of stearic acid by the organic base choline hydroxide[J]. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2009, 338 (1-3) : 129-134. doi: 10.1016/j.colsurfa.2008.04.049
[21]	Klein R, Touraud D, Kunz W. Choline carboxylate surfactants: biocompatible and highly soluble in water[J]. Green Chemistry, 2008, 10 (4) : 433-435. doi: 10.1039/b718466b
[22]	Wang Y, Jiang L, Shen Q, et al. Investigation on the self-assembled behaviors of C18 unsaturated fatty acids in arginine aqueous solution[J]. RSC Advances, 2017, 7 (66) : 41561-41572. doi: 10.1039/C7RA06088B
[23]	Morigaki K, Walde P. Giant vesicle formation from oleic acid/sodium oleate on glass surfaces induced by adsorbed hydrocarbon molecules[J]. Langmuir, 2002, 18 (2) : 10509-10511. doi: 10.1021/la026579r
[24]	Suga K, Yokoi T, Kondo D, et al. Systematical characterization of phase behaviors and membrane properties of fatty acid/didecyldimethylammonium bromide vesicles[J]. Langmuir, 2014, 30 (43) : 12721-12728. doi: 10.1021/la503331r pmid: 25295838
[25]	Rogerson M L, Robinson B H, Bucak S, et al. Kinetic studies of the interaction of fatty acids with phosphatidylcholine vesicles (liposomes)[J]. Colloids and Surfaces B: Biointerfaces, 2006, 48 (1) : 24-34. doi: 10.1016/j.colsurfb.2006.01.001
[26]	Han Y, Chu Z, Sun H, et al. “Green’’ anionic wormlike micelles induced by choline[J]. RSC Advances, 2012, 2 (8) : 3396-3402. doi: 10.1039/c2ra20136d
[27]	Xu H, Du N, Song Y, et al. Spontaneous vesicle formation and vesicle-to-micelle transition of sodium 2-ketooctanate in water[J]. Journal of Colloid and Interface Science, 2018, 509: 265-274. doi: S0021-9797(17)31053-6 pmid: 28915484
[28]	Xu W, Liu H, Song A, et al. Bilayers and wormlike micelles at high pH in fatty acid soap systems[J]. Journal of Colloid and Interface Science, 2016, 465: 304-310. doi: 10.1016/j.jcis.2015.12.006 pmid: 26688122
[29]	Liu L, Yao W, Rao Y, et al. pH-Responsive carriers for oral drug delivery: challenges and opportunities of current platforms[J]. Drug Delivery, 2017, 24 (1) : 569-581. doi: 10.1080/10717544.2017.1279238 pmid: 28195032
[30]	Kuo S, Shen C, Shen C, et al. Role of pH value in clinically relevant diagnosis[J]. Diagnostics, 2020, 10 (2): 107. doi: 10.3390/diagnostics10020107
[31]	Fan Y, Ma J, Fang Y, et al. Neutral and acid-adapted fatty acid vesicles of conjugated linoleic acid[J]. Colloids and Surfaces B: Biointerfaces, 2018, 167: 385-391. doi: 10.1016/j.colsurfb.2018.04.035
[32]	Nakagaki M, Yokoyama S. Acid-catalyzed hydrolysis of sodium dodecyl sulfate[J]. Journal of Pharmaceutical Sciences, 1985, 74 (10) : 1047-1052. pmid: 4078701
[33]	Xu H, Liang X, Zhang Y, et al. An aqueous two-phase system formed in single-component solution of a-ketooctanoic acid[J]. RSC Advances, 2021, 11 (54) : 34245-34249. doi: 10.1039/D1RA06474F
[34]	Xu H, Du N, Song Y, et al. Vesicles of 2-ketooctanoic acid in water[J]. Soft Matter, 2017, 13 (11) : 2246-2252. doi: 10.1039/c6sm02665f pmid: 28255587
[35]	Arnould A, Perez A A, Gaillard C, et al. Self-assembly of myristic acid in the presence of choline hydroxide: Effect of molar ratio and temperature[J]. Journal of Colloid and Interface Science, 2015, 445: 285-293. doi: S0021-9797(15)00035-1 pmid: 25626134

x	pH Window
x	Range	Width
0	7.5~9.1	1.6
0.05	7.4~9.0	1.6
0.1	6.9~8.6	1.7
0.2	6.6~8.2	1.6
0.3	6.1~8.3 1.1~1.7	2.2 0.6
0.4	1.5~7.9	6.4
0.5	1.3~8.2	6.9