Fluorocarbon emulsions as injectable oxygen carriers. Recent progress and perspectives

Abstract

Fluorocarbon emulsions are presently being developed to serve as injectable oxygen carriers (so-called "blood substitutes"). In this approach oxygen is simply dissolved in the liquid carrier and the amount of gas dissolved is proportional to its partial pressure. Increasing the O2-delivering capacity is therefore achieved more easily by increasing the oxygen content of the air breathed by the patient than by increasing the dose of fluorocarbon administered. The absence of a chemical bond between the gas and its carriers allows over 90% of the transported oxygen to be delivered. The fluorocarbon droplets act as oxygen carriers , and also appear to facilitate its diffusion. Chemically and biologically highly inert, fluorocarbons are excreted by exhalation without being metabolized. The first generation of emulsions, exemplified by Fluosol has only limited efficacy due to its low fluorocarbon content, low intravascular persistence and insufficient stability. It has to be stored and distributed frozen, then reconstituted prior to use. Fluosol has nevertheless been licensed by the Food and Drug Administration for use during high risk PTCA. The second generation of injectable fluorocarbon emulsions, exemplified by Oxygent is 4-5 times more concentrated and consequently more efficacious than Fluosol. Considerably more stable, this emulsion can be stored for over one year at 5-8 degrees C and is ready for use. The fluorocarbon used has a significantly shorter organ-retention time. The applications of the present emulsions are still limited by their short intravascular persistence, and are those for which prolonged efficacy is not required, which includes perioperative hemodilution, ischemia, cardioplegia, reperfusion, sensitization of tumors to radio- and chemotherapy, organ preservation and diagnosis. The efficacy of the new emulsions has been established in various animal models. The mild side-effects observed in Phase I clinical trials appear to result from a transient activation of the monocyte/macrophage system and to be suppressed prophylactically by cyclooxygenase inhibitors or corticosteroids. Research is presently oriented towards controlling intravascular persistence better, increasing emulsion stability further, minimizing side-effects and optimizing emulsion characteristics for specific indications.