Pharmacokinetics and biodistribution of paclitaxel loaded in pegylated solid lipid nanoparticles after intravenous administration

Abstract

In an effort to develop an alternative formulation of paclitaxel (PTX) suitable for intravenous administration, PTX-loaded sterically stabilized solid lipid nanoparticles (SLNs) were prepared and their pharmacokinetics and biodistribution were investigated. The pegylated SLNs were comprised of trimyristin (TM) as a solid lipid core and egg phosphatidylcholine and pegylated phospholipid as stabilizers. The prepared pegylated TM-SLNs containing PTX exhibited monodispersed size distribution with 217.4 ± 32.8 nm of mean diameter and 99% of distribution was smaller than 556.2 ± 89.9 nm. After PTX in the pegylated TM-SLNs or commercial product, Taxol®, was intravenously administered into femoral vein of rats, concentrations of PTX in plasma and organs such as liver, spleen, kidney, heart and lung were analyzed by HPLC following liquid extraction. Plasma profile of PTX for pegylated TM-SLNs was similar to that for Taxol®, with no statistically significant difference at each time point, although mean plasma levels of PTX at each point tended to be slightly lower in pegylated TM-SLNs than in Taxol®. PTX in the pegylated TM-SLNs was taken up mainly into reticuloendothelial system showing 8-fold and 3-fold higher levels in liver and spleen, respectively, 8 h after administration compared to PTX in Taxol®. Meanwhile, PTX levels in kidney, heart and lung were not different between two formulations. There were no statistically significant differences in pharmacokinetic parameters. Taken together the results, the pegylated TM-SLNs provided similar circulation compared with commercial formulation, Taxol®.