, Volume 23, Issue 6, pp 1243-1250

Enhanced Oral Paclitaxel Bioavailability After Administration of Paclitaxel-Loaded Lipid Nanocapsules

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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®, Taxol® 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® 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.