Second-Generation Perfluorocarbon Emulsion Blood Substitutes

Abstract

A novel series of perfluorocarbon (PFC) emulsions, based on perfluorodecalin (C₁₀F₁₈) and stabilised with up to 2.5% (w/v) of lecithin have been produced for evaluation as injectable, temporary respiratory gas-carrying blood substitutes. Some formulations contained 1.0% (w/v) of perfluorodimorpholinopropane (C₁₁F₂₂N₂O₃) to retard droplet growth through molecular diffusion (Ostwald Ripening). Other emulsions contained novel, amphiphilic fluorinated surfactants, such as, for example, the monocarbamate, C₈F₁₇C₂H₄NHC(O)(CH₂CH₂O)₂Me (designated compound P6), at 0.1% (w/v) to enhance stability. Emulsions were prepared by homogenisation, were steam sterilisable and were stable for >300 days (25°C). Injection of rats (7.5 ml kg⁻¹ b.w.) with emulsions produced significant (P < 0.05), transient increases in liver and spleen weights. One emulsion inhibited phorbol 12-myristate 13-acetate (PMA)-stimulated, Luminol®-enhanced, chemiluminescence of human polymorphonuclear leucocytes (PMNL) in vitro, suggesting possible applications in ischaemic tissues for suppressing PMNL-mediated inflammation. The P6 fluoro-surfactant inhibited spontaneous platelet aggregation in hirudin-anticoagulated human blood in vitro, suggesting possible applications as an anti-thrombotic agent.