Kashiwagi Hiroshi, Ueno Masaharu
Division of Pharmaceutical Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama City, Japan.
Yakugaku Zasshi. 2008 May;128(5):669-80. doi: 10.1248/yakushi.128.669.
The mechanism of vesicle-to-micelle or micelle-to-vesicle transition was studied in order to control sizes and fluidities of vesicles during periods of preparation. Dependence of particle sizes measured by quasi-elastic light scattering, turbidities, fluidity parameters monitored by ESR spectroscopy, and morphological changes of mixed aggregates of egg yolk phosphatidylcholine (EPC) and a detergent (octylglucoside (OG) or sodium cholate (Na-chol)) on detergent concentration provided a model of vesicle destruction. It possessed three phase transition points, and proceeded in a stepwise fashion: vesicles, small particles containing large amounts of detergents (SUV()), intermediate structures, and mixed micelles. Vesicle formation on removal of detergents from micelles proceeded oppositely. Micelle-vesicle transition mechanism was common to all detergents examined. The feature of the mechanism was the presence of SUV(). Next, SUV() was prepared by adding appropriate amount of a detergent to small unilamellar vesicles obtained by sonication. Time-dependent size growth of the SUV() was remarkable in the case of OG-containing SUV(), but was insignificant in the case of Na-chol-containing SUV(), suggesting the size determining step to be the stage of the SUV(*). The tendency to produce large or small vesicles from micelles was related to the absence or presence, respectively, of a net charge in the detergent molecule. The fluidities of EPC micelles containing small amounts of a detergent possessing a steroidal structure (e.g., Na-chol or CHAPS) were significantly smaller than the corresponding values of a detergent without a steroidal structure (e.g., OG), suggesting a method of control of orderliness of hydrocarbon chains in EPC vesicles.
为了在制备过程中控制囊泡的大小和流动性,对囊泡 - 胶束或胶束 - 囊泡转变的机制进行了研究。通过准弹性光散射测量的颗粒大小、浊度、通过电子自旋共振光谱监测的流动性参数以及蛋黄磷脂酰胆碱(EPC)与去污剂(辛基葡糖苷(OG)或胆酸钠(Na-chol))混合聚集体的形态变化对去污剂浓度的依赖性提供了一个囊泡破坏模型。它具有三个相变点,并以逐步方式进行:囊泡、含有大量去污剂的小颗粒(SUV())、中间结构和混合胶束。从胶束中去除去污剂时囊泡的形成过程则相反。胶束 - 囊泡转变机制对于所有研究的去污剂都是共同的。该机制的特点是存在SUV()。接下来,通过向超声处理得到的小单层囊泡中加入适量去污剂来制备SUV()。对于含OG的SUV(),其大小随时间显著增长,而对于含Na-chol的SUV()则不明显,这表明大小决定步骤是SUV()阶段。从胶束产生大或小囊泡的趋势分别与去污剂分子中净电荷的不存在或存在有关。含有少量具有甾体结构的去污剂(例如Na-chol或CHAPS)的EPC胶束的流动性明显小于不含甾体结构的去污剂(例如OG)的相应值,这表明了一种控制EPC囊泡中烃链有序性的方法。