Submicron Lipid Emulsions containing Amphipathic Polyethylene Glycol for use as Drug-carriers with Prolonged Circulation Time

Submicron-sized lipid emulsions possess many favourable properties as drug-carriers like biocompatibility, physical stability and ease of preparation. The use of colloidal carriers is, however, hampered by their rapid clearance from the circulation. In the present study, this problem was tackled by coating the emulsion droplets with polyethylene glycol modified phosphatidylethanolamine (PEG-PE). Physical stability was obtained by using a mixture of phosphatidylcholine and polysorbate 80 as emulsifying agent. Sonicated preparations with the standard composition; triolein (TO): dipalmitoyl phosphatidylcholine (DPPC): polysorbate 80: PEG-PE at mass ratios of 2: 1: 0.4: 0.1 exhibited a mean particle size of 44 nm (by quasi-elastic light scattering) and an excellent physical stability. In vivo plasma clearance data were obtained by intravenous injection of emulsions into mice. Coating of the emulsion droplets with PEG-PE gave a considerable increase in circulation lifetime. A further notable effect was obtained when the cosurfactant polysorbate 80 was introduced into the system, apparently as a result of decreased particle size. Lipid emulsions with the standard composition showed first order kinetics during 6 h with a circulation half-life of about 3 h. Phospholipid transition temperature and emulsion particle size were found to be important factors while the clearance rate was essentially independent of lipid dose.