Synergistic stabilization of perfluorocarbon‐pluronic F‐68 emulsion by perfluoroalkylated polyhydroxylated surfactants

One of the most serious limitations of the first generation of fluorocarbon emulsions destined to serve as injectable oxygen carriers (blood substitutes) is their insufficient, stability. Considerable stabilization of such emulsions has now been achieved by using a combination of Pluronic F‐68, a polyoxyethylene polyoxypropylene block polymer, and of a perfluoroalkylated polyhydroxylated surfactant (PPFS) comprising a C 6 F 13 or C 8 F 17 fluorophilic tail and a hydrophilic head derived from maltose or xylitol. These new surfactants are either soluble in water or dispersible in an aqueous Pluronic F‐68 solution. The tensions at the surface of these solutions and dispersions and at their interface with a typical fluorocarbon, F‐decalin, are discussed. A strong stabilizing effect on F‐decalin emulsions was obtained when small amounts of PPFS were incorporated, the total amount of surfactant used remaining constant. For 20% w/v emulsions, the maximum stabilizing effect was reached when 20–30% of PPFS were present, resulting after one year at 25°C in an up to 10 times smaller increase in particle size than for a reference emulsion prepared with Pluronic F‐68 alone. The effect is even stronger with more concentrated 50% w/v emulsions, reaching a stabilizing ratio of 17 after one year for a one‐to‐one PPFS/Pluronic F‐68 combination. None of the PPFS, when taken alone, permitted the preparation of stable emulsions. The characteristic U‐shape taken after aging, by the particle size vs PPFS/Pluronic F‐68 ratio curves demonstrates a strong synergistic effect of the two surfactants. They also permitted the selection of optimal formulations for the emulsions. The evolution of the particle sizes against time for such formulations was followed for 20% and 75% w/v concentrated F‐decalin emulsions at 4°C, 25°C and 50°C. The best emulsion in terms of stability was obtained with the xylitol derivative C 8 F 17 CH=CHCH 2 OCH 2 (CHOH) 4 H; most significantly, temperature, from 4 to 50°C, had little or no effect on the aging of this emulsion over a two month period.