Polymer prodrug approaches applied to paclitaxel

Paclitaxel possesses a unique mechanism of drug action as a new class of microtubule stabilizing agent which finally leads to disrupted mitosis and cell death. Recent findings have shown that paclitaxel initiates apoptosis through multiple mechanisms. However, the strong hydrophobicity of paclitaxel drastically limits its use in natural form. In addition, significant toxicity which is mainly ascribed to the non-specific, indiscriminate distribution among the tissues limited the application of paclitaxel in cancer therapy. Therefore, it remains of interest to improve their use by enhancing solubility, selectivity and in vivo delivery by preparing functional prodrugs selectively activable in tumour areas. This article summarizes results and information derived recently from paclitaxel prodrugs based mainly on macromolecular conjugates and their interactions with body fluids. We also explore the potential application of site-specific carriers in the development of tumor-targeting paclitaxel conjugates.