Characterization of fluorocarbon-in-water emulsions with added triglyceride.

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.

Reduction of cerebral infarction using the third circulation.

OBJECTIVE: To ascertain whether ventriculosubarachnoid perfusion of the brain with an oxygen-carrying nutrient emulsion affects the volume of infarction in animals with permanent middle cerebral artery occlusion. DESIGN: Prospective, randomized, controlled trial. SETTING: An animal laboratory in a university setting. SUBJECTS: Twenty-eight closed colony adult cats weighing between 3.5 and 4.5 kg. INTERVENTIONS: Cats were assigned randomly into one of three groups: untreated surgical controls, artificial cerebrospinal fluid (ACSF) perfused, or oxygenated fluorochemical (t-bis perfluorobutylethylene; F44E) nutrient emulsion (OFNE) perfused. The formulation used in this study was developed for clinical use and is currently being used in a phase 1 clinical trial in patients with severe ischemic stroke. Focal cerebral ischemia was induced by permanently clipping the middle cerebral artery via the retro-orbital approach. Treatment was initiated 90 mins postocclusion and continued for 18 hrs. Animals were killed 1 hr after the termination of perfusion, the brains were sectioned and stained with 2,3,5-triphenyltetrazolium chloride, and the infarct area was determined with a computer digitizer. MEASUREMENTS AND MAIN RESULTS: There was a significant difference in cerebral infarct volume in the OFNE-perfused animals compared with the other groups ( p