Enhanced oral paclitaxel bioavailability after administration of paclitaxel-loaded lipid nanocapsules

Purpose: The aim of this study was to evaluate the pharmacokinetics of paclitaxel-loaded lipid nanocapsules (LNC) in rats to assess the intrinsic effect of the dosage form on the improvement of paclitaxel oral exposure. Methods: Paclitaxel-loaded LNC were prepared and characterized in terms of size distribution, drug payload, and the kinetics of paclitaxel crystallization. Taxol (R), Taxol (R) with verapamil, or paclitaxel-loaded LNC were administered orally to rats. The plasma concentration of paclitaxel was determined using liquid chromatography mass spectrometry. Results: The average size of LNC was 60.9 +/- 1.5 nm. The drug payload of paclitaxel was 1.91 +/- 0.01 mg/g of aqueous dispersion. The encapsulation efficiency was 99.9 +/- 1.0%, and 1.7 +/- 0.1% of paclitaxel was crystallized after 24 h. The oral bioavailability of Taxol (R) alone was 6.5%. After oral administration of paclitaxel-loaded LNC or paclitaxel associated with verapamil, the area under the plasma concentration-time curve was significantly increased (about 3-fold) in comparison to the control group (p < 0.05). Conclusions: The results indicated that LNC provided a promising new formulation to enhance the oral bioavailability of paclitaxel while avoiding the use of pharmacologically active P-gp inhibitors, such as verapamil.