Mixed fluorocarbon/hydrocarbon molecular “dowels” allow improved control over concentrated fluorocarbon emulsion particle sizes and stability

Abstract

Highly concentrated (90% w/v, 47% v/v) fluorocarbon/egg yolk phospholipids (EYP) emulsions for oxygen transport and delivery systems (blood substitutes) are presently under development. Primary objectives of the research are to optimally adapt the emulsions characteristics (particle size, size distribution, viscosity, in vivo recognition, etc…) to the specific requirements of each of the targeted applications and to increase the stability of the emulsions for long-term room temperature storage and transportation. A new approach to emulsion stabilization utilizes linear mixed fluorocarbon- hydrocarbon amphiphiles to improve the cohesion between the surfactant film and the fluorocarbon phase [J.G. Riess and M. Postel, Biomat., Art. Cells, Immob. Biotech., (in press)]. The role of the surfactant in lowering the interfacial tension is divided into two complementary contributions, one involving the classical hydrophilic/lipophilic EYP, the other a lipophilic/ fluorophilic surfactant, i.e. the mixed hydrocarbon/fluorocarbon compound. This compound plays the role of a molecular dowel between the fluorocarbon phase and the lipidic fatty acid chains of the EYP membrane. We report here the preparation of stable concentrated fluorocarbon emulsions stabilized by molecular dowels. With one mole of the dowel molecules (C 8H 17CHCHC 8F 17) per mole of EYP, no detectable increase in average particle size has been observed after 9 months of storage at 40 °C, after an initial stabilization period of ca. 20 days. The size of the droplets in the emulsions is directly related to the amount of phospholipids and dowels. For a range of EYP concentration from 0.1 to 4%, it is possible to prepare both very fine emulsions (ca. 0.13 μm post-sterilization) using 4% EYP, as well as much coarser, but nevertheless narrowly distributed and sterilizable emulsions of ca. 2.5 μm in diameter. In that range of concentrations, we have observed a linear variation of droplet diameters of fluorocarbon emulsions stabilized by molecular dowels as a function of the EYP concentration. We will discuss the mechanism of stabilization brought by the molecular dowels in comparison with other additives, which usually operate by slowing down the molecular diffusion process (Ostwald rippening), which is admitted to be the major cause of degradation of fluorocarbon emulsions during ageing.