Design, synthesis and emulsifying properties of new perfluoroalkylated phosphatidylcholines

Abstract

The achievement of fluorocarbon-based injectable O 2 delivery systems and the full exploitation of their potential has established the need for new fluorophilic surfactants and co-surfactants for improving and manipulating the emulsions' characteristics in order to adjust them to specific therapeutic applications. New perfluoroalkylated phospholipids (F-alkylGPCs) have been developped which are structural analog of phosphatidylcholine present in the natural phospholipids used in injectable emulsions. Their synthesis is based on the phosphorylation of rac-1,2-di-(F-alkylacyl)-3-glycerol with 2-bromoethyldichlorophosphate, followed by reaction with an amine. ▪ When taken as the sole surfactant, the new F-alkylGPCs allow the preparation of perfluorodecalin (FDC) emulsions. The efficiency of the emulsifier improves when the perfiuoroalkylated tail length or the Fn/Cm ratio are increased. The most efficient surfactant, compound 2, in spite of its being monodisperse, is as efficient as egg yolk phospholipids (EYP), a mixture of natural phospholipids. The co-surfactant properties of the F-alkylGPCs with EYP are related to the surfactant's total chain length. Compound 4 demonstrated a strong synergistic stabilizing effect with EYP while 3 did not improve the emulsions' characteristics and 2 lead to large particle size emulsions. These results will be rationalized in terms of interactions of the surfactant's perfluoroalkylated tail with the fluorocarbon phase and with the fatty acid chains of the EYP.