Development and in vitro characterization of paclitaxel and docetaxel loaded into hydrophobically derivatized hyperbranched polyglycerols

Abstract In this study we report the development and in vitro characterization of paclitaxel (PTX) and docetaxel (DTX) loaded into hydrophobically derivatized hyperbranched polyglycerols (HPGs). Several HPGs derivatized with hydrophobic groups (C 8/10 alkyl chains) (HPG–C 8/10 –OH) and/or methoxy polyethylene glycol (MePEG) chains (HPG–C 8/10 –MePEG) were synthesized. PTX or DTX were loaded into these polymers by a solvent evaporation method and the resulting nanoparticle formulations were characterized in terms of size, drug loading, stability, release profiles, cytotoxicity, and cellular uptake. PTX and DTX were found to be chemically unstable in unpurified HPGs and large fractions (∼80%) of the drugs were degraded during the preparation of the formulations. However, both PTX and DTX were found to be chemically stable in purified HPGs. HPGs possessed hydrodynamic radii of less than 10 nm and incorporation of PTX or DTX did not affect their size. The release profiles for both PTX and DTX from HPG–C 8/10 –MePEG nanoparticles were characterized by a continuous controlled release with little or no burst phase of release. In vitro cytotoxicity evaluations of PTX and DTX formulations demonstrated a concentration-dependent inhibition of proliferation in KU7 cell line. Cellular uptake studies of rhodamine-labeled HPG (HPG–C 8/10 –MePEG 13 –TMRCA) showed that these nanoparticles were rapidly taken up into cells, and reside in the cytoplasm without entering the nuclear compartment and were highly biocompatible with the KU7 cells.