Polyethylene glycol modified phospholipids stabilize emulsions prepared from triacylglycerol

A stable lipid-based carrier system containing a triacylglycerol core has been developed. This has been achieved by homogenization of corn oil (primarily triacylglycerol) in the presence of phosphatidylcholine (PC), preformed 100 nm liposomes prepared from PC/cholesterol (55: 45; mol:mol) and polyethylene glycol modified phosphatidylethanolamine (PEG2000-PE). The lipid/liposome mixtures were emulsified using a microfluidizer, and the resulting particles could, depending on the phospholipids used and the addition of cholesterol, be designed to exhibit a uniform mean particle size of less than 100 nm (as measured by quasielastic light scattering). The presence of an oil core within the emulsified lipid preparation was confirmed by freeze-fracture and cryoelectron microscopy. Stability of the resulting PEG2000-PE-coated triacylglycerol emulsion was determined by several techniques including (1) time dependent changes in light scatter determined by measuring changes in absorbance at 600 nm (decreases in absorbance are indicative of unstable oil emulsions), (2) column chromatography procedures evaluating the migration of incorporated lipids, specifically PEG2000-PE and triolein, after emulsions were incubated at 37 degrees C in the presence and absence of serum, and (3) in vivo plasma clearance data demonstrating that the lipid mixtures were maintained at ratios specified prior to i.v. administration. This emulsion technology has been used to prepare formulations of several water insoluble compounds, such as the drugs taxol and dibucaine and the lipophilic dye sudan IV.