Filled Vesicles Formed by Phase Transfer of Emulsions or Microemulsions

Abstract

Vesicles or liposomes are of great interest as drug delivery system or simple model for cell membranes. In biological environments vesicles are capable of transporting messenger molecules in high concentrations within a cell. For industrial applications, it is necessary to produce vesicles which are unilamellar, monodisperse, easy to adjust in size, and which can be filled with various types of active compounds. Particularly the defined filling of these tiny compartments has not yet been brought to a large scale. Our research project within the DFG-priority program 1273 (Colloid Process Engineering) was focused on a new method, which can easily be used for the continuous production of such colloidal particles. Moreover, the novel approach allows us to use a large variety of incorporated ingredients. The high encapsulation efficiency in addition with the flexible synthesis facilitates the utilization as a drug carrier system. On grounds of the interesting structure, consisting of an unilamellar surfactant shell, which is swollen with oil, and an enclosed aqueous reservoir (core), the produced colloidal particles may alternatively be denoted as a special case of water-in-water-emulsions. The synthesis of these particles occurred in three steps. First, a water phase was covered by an oil phase containing surfactants or lipids. A water-in-oil emulsion or microemulsion was then added to the oil phase. In the third step the phase transfer of aqueous droplets from the oil phase into the underlying water phase was stimulated by sedimentation, flow, electric forces or centrifugation processes. During this phase transition a small amount of the organic solvent was entrapped in the ultra-thin membranes and influenced the properties of the filled, vesicular structures. The thin layer of organic solvents reduced the diffusion processes from the core of the vesicles into the surrounding water phase. This might be of special advantage for the encapsulation of water soluble ingredients as drugs or other interesting compounds. It also offers the opportunity, to store oil soluble substances in the swollen membranes of the vesicles. On the other hand the thin oil layers surrounding the vesicles induced creaming processes and influenced the stability of these aggregates. For all applied experimental techniques we systematically measured the encapsulation capacity, the size of the filled vesicles, the amount of entrapped oil within the membranes and the stability of these aggregates. It turned out, that the jet-stream and the electrospray technique provided the best results concerning long-term stability, vesicle production and encapsulation efficiency. Due to the broad spectrum of different applications, we could use the phase-transfer process for the production of tailor-made, filled and swollen vesicles, which showed interesting properties.