A submicron lipid emulsion coated with amphipathic polyethylene glycol for parenteral administration of paclitaxel (Taxol)

Paclitaxel is a promising anticancer agent with poor solubility in water and requires a suitable formulation for intravenous administration. Presently paclitaxel is formulated for clinical use in ethanol and Cremophor EL (Diluent 12), a solvent system associated with severe adverse effects. In this study paclitaxel was entrapped in lipid emulsion droplets with triolein as oil core and dipalmitoyl phosphatidylcholine as the principal emulsifier. The emulsion was further stabilized with polysorbate 80 and polyethylene glycol-dipalmitoyl phosphatidylethanolamine. The drug-emulsion droplets (diameter about 40 nm) were physically and chemically stable during several months at 4 degrees C. Lyophilized preparations in 5% glucose were completely restored by distilled water. Studies of the integrity of the drug-emulsion showed a release of the drug from emulsion globules and surface transfer was found to be the major mechanism for cellular uptake. The in-vitro antiproliferative activity of paclitaxel against T-47D cells was retained by the drug-emulsion with an ID50 value of 7 nM compared to 10 and 35 nM for paclitaxel in liposomes and Diluent 12, respectively. Long-circulating submicron lipid emulsions may prove useful, not only for replacement of the more toxic Cremophor EL vehicle, but also by improving the distribution of the drug to the tumour.