Preliminary in vivo studies of a new lecithin-based formulation of paclitaxel

Abstract

Amorphous paclitaxel dissolves rapidly (1 mg mL⁻¹) in an isotonic aqueous dispersion of egg lecithin (5% w/w), a new biocompatible submicron drug carrier consisting of structured aggregates with average size 0.5 µm. The solution is physically stable for at least 24 h and can be administered as an intravenous infusion. After a 5 h infusion in rabbits (0.66 mg kg⁻¹ h⁻¹), changes in blood morphology were comparable to those observed in rabbits that received the commercial product Taxol®. No changes in the enzyme profiles (alanine/aspartate aminotransferase or alkaline phosphatase) were observed. However, during infusion of the new formulation plasma concentration of paclitaxel (292 ± 182 ng mL⁻¹) was lower than observed after Cremophor-containing Taxol® (540 ± 262 ng mL⁻¹). This result may indicate that the tissue distribution is different for the two drug formulations. Daily intraperitoneal administrations (3 doses/day) in mice demonstrated that the new carrier solution was non-toxic and, relative to Taxol, the new formulation exhibited similar or less toxicity.

• Paclitaxel
• lecithin
• infusion
• toxicity
• solubilization
• electron microscopy