Characterization of Fluorocarbon-in-Water Emulsions With Added Triglyceride

Abstract

Fluorocarbon-in-water emulsions are being explored clinically as synthetic oxygen carriers in general surgery. Stabilizing fluorocarbon emulsions against coarsening is critical in maintaining the biocompatibility of the formulation following intravenous administration. It has been purported that the addition of a small percentage of long-chain triglyceride results in stabilization of fluorocarbon emulsions via formation of a three-phase emulsion. In a three-phase emulsion, the triglyceride forms a layer around the dispersed fluorocarbon, thereby improving the adhesion of the phospholipid surfactant to the dispersed phase. In the present study, we examined the effect of triglyceride addition on the physicochemical characteristics of the resulting complex dispersion. In particular, we examined the particle composition and stability of the dispersed particles using a method which first fractionates (classifies) the different particles prior to sizing (i.e., sedimentation field-flow fractionation). It was determined that the addition of a long-chain triglyceride (soybean oil) results in oil demixing and two distinct populations of emulsion droplets. The presence of the two types of emulsion droplets is not observed via light scattering techniques, since the triglyceride droplets dominate the scattering due to a large difference in the refractive index between the particles and the medium as compared to fluorocarbon droplets. The growth of the fractionated fluorocarbon emulsion droplets was followed over time, and it was found that there was no difference in growth rates with and without added triglyceride. In contrast, addition of medium-chain-triglyceride (MCT) oils results in a single population of emulsion droplets (i.e., a three-phase emulsion). These emulsions are not stable to droplet coalescence, however, as significant penetration of MCT into the phospholipid lipid interfacial layer results in a negative increment in the monolayer spontaneous curvature, thereby favoring water-in-oil emulsions and resulting in destabilization of the emulsion to the effects of terminal heat sterilization or mechanical stress.

Fluorine‐containing nanoemulsions for MRI cell tracking

“…However, this is far from being a rule and surfactants can play a significant role in emulsion stability. Possible methods to decrease Ostwald ripening, for example, include the addition of water-insoluble oils such as a long triglyceride to the nanoemulsion62 or the use of longer chain perfluorocarbons 63…”

Hollow Nanospheres with Fluorous Interiors for Transport of Molecular Oxygen in Water

“…Although the ultra‐hydrophobic nature of SFCs often benefits their application, it also makes direct incorporation of fluorous compounds into water‐based systems impossible. A wide range of compatibilizing agents/systems have been proposed for suspending SFCs in water, including lipids, block copolymers, and proteins. The oleophobicity of fluorous compounds tends to destabilize SFC emulsions, thus rendering common dispersion approaches only a temporary success.…”

“…The oleophobicity of fluorous compounds tends to destabilize SFC emulsions, thus rendering common dispersion approaches only a temporary success. Incorporation of SFC liquids into self‐assembled polymer nanocapsules led to stable and useful formulations . The walls of such capsules are impermeable to gases, which limits the applicability of these materials.…”

“…[5] SFC liquids, polymers, and emulsions have found applications in catalysis of aerobic oxidations, [6][7] in oxygenation of submerged aerobic cultures, [8] as blood substitutes [3,9] and as media for liquid ventilation [3,10] and oxygenation in lung injury treatment [11] .Although the ultra-hydrophobic nature of SFCs often benefits their application, [3,[12][13] it also makes direct incorporation of fluorous compounds into water-based systems impossible. A wide range of compatibilizing agents/systems have been proposed for suspending SFCs in water, including lipids, [14] block copolymers, [7,15] and proteins [16] . The oleophobicity of fluorous compounds tends to destabilize SFC emulsions, [17][18][19] thus rendering common dispersion approaches only a temporary success.…”

Fluorophilicity of alkyl and polyfluoroalkyl nicotinic acid ester prodrugs

“…Fluorocarbons and perfluorinated moieties have demonstrated potential for a variety of novel industrial [1, 2] and pharmaceutical applications, including liquid ventilation therapy, diagnostic ultrasound imaging and as blood contrast agents [3-8]. The potential to extend fluorinated solvent applications to drug delivery is limited by the poor solubility of typical hydrocarbon-based polar and non-polar pharmaceuticals in these solvents [9, 10].…”