Mechanism of micelle-vesicle transformation and control of vesicular sizes and properties

Abstract

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 step-wise 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. © 2008 The Pharmaceutical Society of Japan.