LARGE DISK-SHAPED STRUCTURES (DISCOMES) IN NONIONIC SURFACTANT VESICLE TO MICELLE TRANSITIONS

Addition of surfactants to vesicular dispersions can lead to solubilization of the vesicles and their subsequent translation into mixed micellar systems (Kim and Kim, 1991). We have found that large discoid structures exist under certain conditions of the phase diagram of nonionic surfactant vesicles prepared from a hexadecyl diglycerol ether (C16G2), cholesterol, and dicetyl phosphate (DCP) in the molar ratio 69:29:2 by mechanical shaking and sonication followed by incubation with a soluble polyoxyethylene cholesteryl ether, Solulan C24, at 74-degrees-C. Turbidity measurements were made at 350 nm. Break points were identified in the turbidity vs Solulan C24 concentration plots, where sharp differences in the turbidity of the dispersion occur, and are indicative of a change in phase. A partial phase diagram was constructed for the system in which four phases can be identified: a lamellar phase, a micellar phase, an uncharacterized phase, and a novel phase we have called the "discome" phase. Dispersions in the discome phase comprised large discomes (volume distribution mean diameter 12-60 mum). Lipids in the proportions found in the discome phase (i.e., C16G2:cholesterol:Solulan C24:DCP 49:19.5:29:2), when sonicated, produced discomes, formation of which was accompanied by a slow increase in particle size of the dispersion immediately after sonication. Discomes entrap water soluble solutes. When lipid films are hydrated with 8 mM 5(6)-carboxyfluorescein (CF), aqueous entrapment values of 1.209 +/- 0.97 L/mol lipid were recorded. The release of CF over a 24-h period at room temperature was measured. Discomes were found to retain 50% of the entrapped CF. The drug delivery potential of these discomes in the field of ophthalmology is highlighted.