Enhanced oral paclitaxel bioavailability after administration of paclitaxel-loaded lipid nanocapsules.
OBJECTIVE
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.
Peltier
Sandra
S
U646, Angers, F-49100 France, Université d'Angers, Angers, F-49035, Cedex1, France.
Oger
Jean-Michel
JM
Lagarce
Frédéric
F
Couet
William
W
Benoît
Jean-Pierre
JP
D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D004339:Drug Compounding; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008055:Lipids / Q000737:chemistry; D008081:Liposomes; D008297:Male; D049329:Nanostructures / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000972:Antineoplastic Agents, Phytogenic; D008055:Lipids; D008081:Liposomes; D017239:Paclitaxel