Phase behavior of fluorocarbon and hydrocarbon double-chain hydroxylated and galactosylated amphiphiles and bolaamphiphiles. Long-term shelf-stability of their liposomes

This paper describes the morphological characterization, by freeze-fracture electron microscopy, and the thermotropic phase behavior, by differential scanning calorimetry and/or X-ray scattering, of aqueous dispersions of var ious hydroxylated and galactosylated double-chain amphiphiles and bolaamphi philes, several of them containing one or two hydrophobic fluorocarbon chai ns. Colloidal systems are observed in water with the hydroxylated hydrocarb on or fluorocarbon bolaamphiphiles only when they are dispersed with a co-a mphiphile such as rac-1,2 dimyristoylphosphatidylcholine (DMPC) or rac-1,2- distearoylphosphatidylcholine (DSPC). Liposomes are formed providing the re lative content of bolaamphiphiles does not exceed 20% mel. Most of these li posomes can be thermally sterilized and stored at room temperature for seve ral months without any significant modification of their size and size dist ribution. The hydrocarbon galactosylated bolaamphiphile HO[C24][C12]Gal for ms in water a lamellar phase (the gel to liquid-crystal phase transition is complete at 45 degrees C) and a Im3m cubic phase above 47 degrees C. The f luorocarbon HO[C24][F6C5]Gal analog displays a more complex and metastable phase behavior. The fluorinated non-bolaform galactosylated [F8C7][C16]AEGa l and SerGal amphiphiles form lamellar phases in water. Low amounts (10% mo lar ratio) of the HO[C24][F6C5]Gal or HO[C24][C12]Cal bolaamphiphiles or of the single-headed [F8C7][C16]AEGal improve substantially the shelf-stabili ty of reference phospholipon/cholesterol 2/1 liposomes. These liposomes whe n co-formulated with a single-headed amphiphile from the SerGal series are by far less stable. (C) 1999 Elsevier Science Ireland Ltd. All rights reser ved.