Preparation and evaluation of paclitaxel-containing liposomes

Paclitaxel, an antitumoral drug, is poorly soluble in aqueous media. Therefore, in a commercialised formulation (Taxol®), paclitaxel (30 mg active compound) is dissolved in polyethoxylated castor oil (Cremophor® EL) and ethanol. After dilution of Taxol® in aqueous media paclitaxel tends to precipitate. Several side effects, attributed to the surfactant Cremophor® EL, occur, e.g. bronchospasm, hypotension, neuro- and nephrotoxicity, and anaphylactic reactions. To eliminate these side effects, the solubility of paclitaxel was enhanced using liposomes instead of Cremophor® EL. The amount of entrapped paclitaxel in crystal-free liposomes was 0.5 mg/ml liposome suspension, i.e. almost 85 times the native solubility. Thus, 30 mg paclitaxel had to be dissolved in 60 ml liposome suspension, of either multi-lamellar vesicles (MLV's) or of small unilamellar vesicles (SUV's) with 5% sucrose as cryoprotector. No precipitation was observed after dilution of the MLV-formulation with (physiological) water or with 5% aqueous dextrose solution, which proves their suitability for administration with perfusions. The chemical stability of paclitaxel in the prepared MLV's stored at 4 °C was demonstrated during a period of 5 months. The chemical degradation to conjugated dienes and hydroperoxides, two oxidative degradation products of EPC, was negligible (less than 1%).