Development and characterization of biodegradable chitosan films for local delivery of Paclitaxel

Intratumoral and local drug delivery strategies have gained momentum recently as a promising modality in cancer therapy. In order to deliver paclitaxel at the tumor site in therapeutically relevant concentrations, chitosan films were fabricated. Paclitaxel could be loaded at 31% wt/wt in films, which were translucent and flexible. Physicochemical characterization of paclitaxel via thermal, spectroscopic, x-ray diffraction, and electron microscopy techniques revealed information on solid-state properties of paclitaxel as well as chitosan in films. While chitosan was in amorphous form, paclitaxel seemed to be present in both amorphous and crystalline forms in film. The polymeric dispersion of paclitaxel in poloxamer formed fibrous structures generating discontinuities in the film matrix, thereby leading to the introduction of perturbations in the packing arrangement of polymer chains. These films released only 10% to 15% of loaded paclitaxel by a burst effect under in vitro testing conditions, with lysozyme having no effect on the release. However, films softened after implantation in mice and lost integrity over time. The implantable delivery system is not only biodegradable but also well tolerated in vivo and hence, biocompatible as revealed by histological studies. The lack of formulation-induced local inflammatory responses of paclitaxel chitosan films suggests a new paradigm for localized chemotherapy based on implantable systems.