Functionalized Pluronic-b-poly(ε-caprolactone) based nanocarriers of paclitaxel: solubilization, antiproliferative efficacy and in vivo pharmaceutic kinetics

Novel nanocarriers for paclitaxel (PTX) were developed based on Pluronic-b-poly(ε-caprolactone) bearing pendant benzyl-oxycarbonylmethyl (BOM) groups and carboxyl groups (Pluronic-b-P(CL-co-BCL), FB)/(Pluronic-b-P(CL-co-CCL), FC). The formation and the physicochemical properties of paclitaxel-loaded polymeric micelles, including FB/PTX micelles and FC/PTX micelles, were investigated by various methods. The results demonstrated that paclitaxel was amorphous in the micellar core and the micelles were on nanoscale. Besides the hydrophobic-hydrophobic interaction in both micelles, there was π-π interaction in the FB/PTX micelles while hydrogen bonding interaction existed in the FC/PTX micelles. Thus the different interaction between the drug and the polymer endowed the polymers with different binding forces which determined the various properties of the nanocarriers. The comparative study revealed that the compatibility was improved due to the introduction of the pendant groups according to the calculation based on the Flory-Huggins interaction parameter (χ ). The two nanocarriers also displayed high encapsulation efficiency, which could reach 88.61 ± 5.33% and 90.7 ± 2.08%, and they could also provide a continuous and sustained in vitro PTX release and the release half time was greatly enhanced in comparison with commercial Taxol®. Furthermore, the in vitro anti-tumor efficiency revealed that the FC PTX-loaded micelles had the best anti-tumor activity against C6 glioma cells inducing cell apoptosis and the in vitro blood compatibility and the in vivo long-circulation characteristics were well retained for the FB and FC PTX-loaded micelles in comparison with the original Pluronic-b-PCL. Therefore, these findings indicated that the functionalized Pluronic-b-poly(ε-caprolactone) micelles would be efficient nanocarriers for paclitaxel.