Amphiphilic dextran-graft-poly(epsilon-caprolactone) films for the controlled release of paclitaxel

Amphiphilic graft copolymers with dextrans as the main chains and poly(epsilon-caprolactone) as the side chains were synthesized by solution polymerization in dimethyl sulfoxide using stannous 2-ethylhexanoate as a catalyst. The copolymers were characterized with nuclear magnetic resonance spectroscopy and gel permeation chromatography. Paclitaxel loaded copolymer films were prepared using a solution cast method. In vitro release rates were influenced by both the initial paclitaxel loading and the morphology of the films. The films with paclitaxel loadings up to 10% (w/w) showed a single-phase morphology when dry. However, paclitaxel crystallization occurred in the films with high loadings (5 and 10%) upon incubation in phosphate buffered saline at 37 degrees C. The crystals had a spherulitic structure and were found to be paclitaxel dihydrate based on X-ray diffraction analysis. The formation of paclitaxel dihydrate in the films produced a marked effect on the in vitro release rates.