Pharmacokinetic Behavior and Biodistribution of Paclitaxel-Loaded Lipid Nanosuspension

Abstract

In this study, paclitaxel-loaded lipid nanosuspension (PxLN) was prepared and the in vivo profiles after intravenous administration in rats were investigated. We compared the manufacturing processes depending on the temperature: PxLN-H for a hot homogenization process and PxLN-C for solidification of lipid-drug mixtures by liquid nitrogen. Both formulations showed submicron size distribution and the similar drug loading efficiency of about 70%. In vitro release of PxLNs and Taxol® performed by a dialysis diffusion method showed similar pattern for PxLN-H and Taxol®, but the reduced release profile for PxLN-C. PxLN or Taxol® was intravenously administered to the rats at a dose of 5 mg/kg as paclitaxel. The drug in blood samples were assayed by the HPLC/MS/MS method. The AUCt of PxLN-H was 3.4-fold greater than that of Taxol®. PxLN-H gave higher biodistribution in all tissues than did Taxol®. In addition, it maintained the higher drug concentration for 12 h. This lipid nanosuspension might be a promising candidate for an alternative formulation for the parenteral delivery of poorly water-soluble paclitaxel.