Effect of composition on biological fate of oil particles after intravenous injection of O/W lipid emulsions

Plasma concentrations of oil particles after intravenous injection of oil-i n-water (O/W) lipid emulsions were monitored based on the plasma concentrat ion of phospholipids (PL) and triglycerides (TG), and the light scattering intensity (LSI) of plasma. Previously, we found that their time profiles af ter injection of the standard O/W lipid emulsion composed of soybean oil (S O) and egg yolk phosphatides (EYP) were similar and suggested that the oil particles with diameter of about 200 nm were entrapped by reticuloendotheli al system (RES). Herein, in order to develop a delivery system to avoid the RES uptake by using the lipid emulsions, biological fate of lipid emulsion s with oil particles of various sizes or those emulsified by surfactants wi th polyoxyethylene segments were subjected to the investigations. Lipid emulsions with oil particles of various sizes (about 150-550 nm) were prepared by altering EYP content. The oil particles were stable in plasma in vitro, but oil particle size decreased time-dependently after intravenou s injection. Plasma clearance of oil particles depended on their initial si ze and nias decreased by pretreatment with dextran sulfate 500 (DS500), a k nown RES suppressor, These results suggested that oil particles are still e ntrapped by RES, even for small-sized oil particles (about 150 nm). Lipid e mulsion with small-sized oil particles was also prepared using medium chain triglycerides. The oil particles were stable in vitro, but the time profil es of plasma concentrations of PL and TG, and LSI of plasma were different, and oil particle size decreased time-dependently after intravenous injecti on. Plasma clearance of the oil particles also depended on their initial si ze and was decreased by DS500, suggesting that in vivo instability could be due to RES-mediated processes. Artificial surfactants with polyoxyethylene segments, HCO-60 (HCO60) and polysorbate 80 (PS80), were used for RES avoi dance. HCO60 resulted in drastic reduction of the plasma clearance of the o il particles for both lipid emulsions composed of soybean oil and medium ch ain triglycerides. The lime-dependent decrease of oil particle size after i ntravenous injection was marginal. In contrast, PS80 could not prolong the circulation time of the oil particles, and their size decreased time-depend ently after intravenous injection.