Emulsion perfluorochemical

C.S. Lai, S. Stair, H. Miziorko, J.S. Hyde, Effect of oxygen and the spin label TEMPO-Laurate on F and proton relaxation rates of the perfluorochemical blood substitute FC-43 emulsion, J. Magn. Reson. 57 (1984) 447-452. 

Perfluorocarbons. In 1966, it was demonstrated (27) that a laboratory mouse could survive total immersion in a perfluorochemical (PFC) solution. This material, similar to commercial Teflon, is almost completely inert and is insoluble in water. A water-soluble emulsion was prepared that could be mixed with blood (28), and in 1968 (29) the blood volume in rats was completely replaced with an emulsion of perfluorotributylamine [311-89-7], C12F27N. The animals survived in an atmosphere of 90—100% 02 and went on to long-term recovery. However, the 02 content of the perfluorochemicals has a linear dependence on the partial pressure of oxygen, P, as can be seen in Figure 1. The very high 02 tension required to transport physiologic amounts of 02 (12) and the propensity of the perfluorocarbon to be taken up by the reticuloendothelial cells were considered to be severe limitations to the development of clinically useful perfluorocarbon blood substitutes (30). 

Medical Applications of Perfluorochemicals in Other Forms than Emulsions ... 

Riess, J.G. Le Blanc, M. Preparation of perfluorochemical emulsions for biomedical use principles, materials and methods. In Blood Substitutes Preparation, Physiology, and Medical Applications Lowe, K.C., Ed. Ellis Horwood Ltd. Chichester, 1988 94-129. 

Naito, R. Yokoyama, K. Perfluorochemical blood substitutes. In FC-43 Emulsion, Fluosol-DA, 20% and 35% Green Cross Corp. Osaka, Japan, 1978, 1981. 

Mitsuno, T. Ohyanagi, H. Yokoyama, K. Suyama, T. Recent studies on perfluorochemical (PEC) emulsion as an oxygen carrier in japan. Biomat. Artif. Cells Artif Organs 1988, 16, 365-373. 

Goodin, T.H. Grossbard, E.B. Kaufman, R.J. Richard, T.J. Kolata, R.J. Allen, J.S. Layton, T.E. A perfluorochemical emulsion for prehospital resuscitation of experimental hemorrhagic shock a prospective, randomized, controlled study. Crit. Care Med. 1994, 22, 680-689. 

There are additional constraints when manufacturing parenteral emulsions that must be sterile and of fine particle size. Perfluorochemical and fat emulsions are usually prepared by homogenization at high temperature and pressure, as a large output of energy is required to produce droplet sizes considerably less than 1 pm. Although heat sterilization is widely used, this places a severe test on the stability, and emulsions are sometimes prepared from sterile components under strict aseptic conditions and further sterilized by filtration. ... 

T Mate, S Rockwell. Perfluorochemical emulsions do not affect bone marrow radiosensitivity. American Society of Therapy Radiation Oncologists Meeting, Washington, DC, 1984. 

Maugh, H., 1973, Perfluorochemical emulsions promising blood substitute. Science 179 669-672. 

Several pharmaceutical products are formulated as emulsions (1) Parenteral emulsion systems, e.g. parenteral nutritional emulsions, lipid emulsions as drug carriers (2) Perfluorochemical emulsions as artificial blood substitute (3) Emulsions as vehicles for vaccines (4) topical formulations, e.g. for treatment of some skin diseases (dermatitis). 

Development of more concentrated injectable perfluorochemical emulsions has extended their diagnostic and therapeutic applications in medicine. Fluoro-... 

Perfluorochemical oxygen earners are not soluble in water. Therefore, perfluori-nated chemicals cannot be administered in the pure form but have to be converted to an aqueous emulsion. A surfactant, selected for its effectiveness and biochemical compatibility, serves as an emulsifier. Osmolarity and oncotic pressures are adjusted by adding electrolytes and oncotic agents, such as hydroxyethyl starch. Nutrients, thrombolytic agents, therapeutic agents, and other additives may be included in the emulsion, depending on the particular clinical application of the emulsion. 

Clinical tests of perfluorochemical oxygen carriers revealed three major problems (1) insufficient stability evidenced by coarsening of the emulsion, (2) toxicity, and (3) unsatisfactory retention time of the fluorochemical in blood and in organs. The toxicity and stability are to some extent related. The biocompatibility of perfluorochemical emulsions is impaired by an increase in particle size [35]. The coarsening of fluorochemical emulsions has been attributed the progressive increase in particle size to Ostwald ripening [94-99]. The diameter profiles for the emulsified perfiuorocarbon droplets in Fluosol-DA and Fluosol 43 have been determined by sedimentation field-flow fractionation [96]. 

A strategy for solving these problems is to prepare a stable emulsion by using an effective biocompatible emulsifier. The retention time can be hopefully adjusted by fine-tuning of the surfactant structure. Tsuda et al. [70] have suggested that the efficacy of a perfluorochemical and its retention time in blood depend on the in vivo stability of the emulsion in circulating blood. 

The properties of a perfluorochemical emulsion depend critically on the surfactant used for emulsification. A surfactant used as an emulsifier in fluorochemical blood substitutes has to meet several criteria (1) provide a fine stable emulsion (2) be nontoxic, nonmutagenic, and nonhemolytic (3) be compatible with blood and endothelial cells (4) be pharmacologically, physiologically, or biochemically inactive and (5) either be excreted unchanged or in the form of harmless metabolites [41]. 

The search for stable perfluorochemical emulsions for biomedical applications has included microemulsions formed by fluorinated surfactants (see Section 4.8). Microemulsions form spontaneously, are thermodynamically stable, and have a small particle size. However, microemulsions have shared with coarser emulsions the toxicity problems associated with fluorinated surfactants. The early microemulsions made with fluorinated surfactants were toxic and viscous. 

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