Polyphosphoester-based Paclitaxel Complexes: Biological Evaluation.

ABSTRACT

BACKGROUND: Polymer drug delivery systems designed to reduce systemic side-effects are clinically important. Polyphosphoesters are biodegradable polymers with versatile structure that could afford reactive sites or polar functions for drug immobilization. MATERIALS AND METHODS: The drug-polyphosphester systems were characterized by nuclear magnetic resonance and infrared spectroscopy, differential scanning calorimetry and dynamic light scattering. In vitro and in vivo experiments were performed to assess the biological activity of the immobilized drug. RESULTS: Two water-soluble polyphosphoester-based delivery systems of paclitaxel were synthesized. The conjugate with paclitaxel covalently bonded to the polymer, had attenuated activity in vitro. The second system comprised of macromolecular aggregates incorporating the drug via hydrogen bonding. The physical complex achieved a certain level of antitumor activity in vivo and no decrease of body weight - evidence for reduction of the systemic toxic effect associated with paclitaxel treatment. CONCLUSION: The physical complex was found to be a promising carrier for delivery of toxic anticancer agents, e.g. paclitaxel.