α-Tocopherol succinate-modified chitosan as a micellar delivery system for paclitaxel: Preparation, characterization and in vitro/in vivo evaluations

alpha-Tocopherol succinate hydrophobically modified chitosan (CS-TOS) containing 17 alpha-tocopherol groups per 100 anhydroglucose units was synthesized by coupling reaction. The formation of CS-TOS was confirmed by H-1 NMR and FT-IR analysis. In aqueous medium, the polymer could self-aggregate to form micelles, and the critical micelle concentration (CMC) was determined to be 5.8 x 10(-3) mg/ml. Transmission electron microscopy (TEM) observation revealed that both bare and paclitaxel-loaded micelles were near spherical in shape. The mean particle size and zeta potential of drug-loaded micelles were about 78 nm and +25.7 mV, respectively. The results of DSC and XRD analysis indicated that paclitaxel was entrapped in the micelles in molecular or amorphous state. In vitro cytotoxicity and hemolysis study revealed the effectiveness and safety of this delivery system, which was further confirmed by the in vivo antitumor evaluations. It can be concluded that the CS-TOS was a potential micellar carrier for paclitaxel. (C) 2011 Elsevier B.V. All rights reserved.