Long-circulating emulsions (oil-in-water) as carriers for lipophilic drugs

Abstract

Purpose: Rapid clearance of parenterally administered oil-in-water emulsions from blood by the reticuloendothelial system (RES), mainly macrophages of the liver and spleen, has been one of the major obstacles for delivering lipophilic drugs to cells other than those in the RES. The purpose of this study therefore is to overcome this problem and develop emulsions that will have prolonged blood circulation time.

Methods: A series of amphipathic polyethylene-glycol (PEG) derivatives have been included as co-emulsifier into emulsions composed of Castor oil and phosphatidylcholine. The effect of amphipathic PEG on reducing the RES uptake and prolonging the blood circulation of the emulsion particles has been tested in vivo using mice as an animal model.

Results: Inclusion of PEG derivatives such as Tween-80 or dioleoyl N-(monomethoxy-polyethyleneglycol succinyl)phosphotidylethanolamine (PEG-PE) into emulsions composed of Castor oil and phosphatidylcholine decreases the RES uptake and increases blood residence time of the emulsions. The activity of PEG derivatives in prolonging the circulation time of emulsions depends on the PEG chain length (PEG2000 > PEG5000 > PEG1000, Tween-80) and the PEG density on emulsion surface.

Conclusions: Inclusion of amphipathic PEG as emulsifier into oil-in-water emulsions is a very effective method to prolong the blood half life of the emulsions. Emulsions with long circulating half life in blood should be very useful as a delivery vehicle for lipophilic drugs.