Nanodelivery Strategies in Breast Cancer Chemotherapy
Taxanes (paclitaxel (PTX)) and anthracyclines are important in the treatment of breast cancer, both in the adjuvant and metastatic settings. Combination therapy with anthracyclines and PTX has been shown to produce significant improvements in survival, but can be associated with significant side effects. By altering the plasma pharmacokinetics and tissue distribution, new anthracycline and PTX nanoparticle formulations such as pegylated liposomal doxorubicin HCl (Doxil®), albumin-bound PTX (Abraxane®), and non-biological, polymeric micellar formulation of PTX (Genexol-PM®) may improve efficacy and reduce the toxicities of these treatment regimens. Unlike the solvent-based PTX formulation (Taxol®), both Abraxane® and Genexol-PM® allow higher dosing of PTX, resulting in improved therapeutic efficacy and comparable overall safety. The higher maximum tolerated dose is attributed to the differences in pharmacokinetics: higher systemic clearance and volume of distribution. In contrast to Taxol®, Genexol-PM® maintained dose proportionality up to 435 mg m−2, and unlike Abraxane®, which displayed a rapid increase in toxicity at doses above 300 mg m−2, Genexol-PM® displayed dose-limiting toxicity only at doses above 400 mg m−2. Unlike Abraxane®, Genexol-PM® is free of human serum albumin, allows simple handling and preparation procedures and broader storage conditions. This chapter addresses these three nanoparticle platforms and the rationale for the evolution of clinically approved PTX nanocarriers with a special emphasis on Genexol-PM® for the treatment of solid tumors, including breast cancer.