Polymorphic phase behavior of fluorocarbon double-chain phosphocholines derived from diaminopropanol, serine and ethanolamine and 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, of aqueous dispersions of various fluorocarbon/fluorocarbon or mixed fluorocarbon/hydrocarbon double-chain 2,3- or 1,3-diamidopropano-, diamidoserino- or amidoethyl-phosphocholines (PC). These fluorinated PCs form lamellar phases and liposomes, as their ester or ether glycerol-based analogs. The effects on the thermodynamic parameters associated with these lamellar phases of several structural elements-chemical junction (secondary CONHR or tertiary CONRR), connecting unit (diamino-propanol, serine or ethanolamine), number and length of the perfluoroalkylated chains, length of the fluorinated tail and hydrocarbon-are discussed. These data are compared with those reported for fluorocarbon or hydrocarbon glycerophosphocholines and hydrocarbon diamidophosphocholines, and for sphingomyelins. Most of the liposomes formed from the fluorinated amido-connected PCs display a remarkable long-term shelf stability: they can be thermally sterilized and stored at room temperature for several months without any significant modification of their size and size distribution. (C) 1997 Elsevier Science Ireland Ltd.