Preclinical evaluation of efficacy and stability of docetaxel micelle-encapsulated by a tripodal cyclotriphosphazene amphiphile

Docetaxel formulated by micelle-encapsulation using a tripodal cyclotriphosphazene amphiphile [NP(MPEG750)(GlyPheLeu)2Et]3 (CP750) was named “Phostaxel” and compared in efficacy and stability with Taxotere® formulated using the surfactant polysorbate 80, which is currently in clinical use. Phostaxel has always shown better efficacy than Taxotere® in various xenograft trials at the same dosage and administration schedule against the tumor cell lines tested. The better efficacy of Phostaxel could be explained based on the difference in pharmacokinetic and biodistribution profiles of Phostaxel and Taxotere®. Phostaxel exhibited significantly slower clearance rate and larger AUClast value compared with Taxotere®. Phostaxel has also shown higher DTX distribution in tumor than Taxotere®. In addition, Phostaxel displayed better solution stability compared with Taxotere® both in distilled water and in saline solution at room and refrigerator temperatures.