Particle size analysis of perfluorocarbon emulsions in a complex whole blood matrix by sedimentation field-flow fractionation

The goal of this study was to show that sedimentation field-flow fractionation (SdFFF) could be used to study changes in the particle size distribution of perfluorocarbon (PFC) emulsion droplets in ex vivo whole blood samples. A PFC emulsion containing 40% w/v perfluorooctyl bromide (PFOB), 20% w/v perfluorodecyl bromide (PFDB), and 6% w/v egg yolk phospholipid (EYP) was manufactured by high pressure homogenization. The emulsion was infused intravenously to rats at a dose of 2.7 g PFC/kg body weight. Blood samples were collected at 0, 3, 6, and 24 h and analyzed (without additional sample manipulation) by SdFFF. Excellent chromatographic separation between the blood components and PFC emulsion droplets was achieved. After infusion, the particle size distribution broadened slightly. With time, the larger sized droplets were selectively removed by circulating monocytes and tissue resident macrophages of the reticuloendothelial system, causing the particle size distribution to shift to lower median diameters. SdFFF is an excellent technique for studying the in vivo stability of colloidal drug particles following intravenous administration. (C) 2003 Elsevier B.V. All rights reserved.