Development, Optimization and Absorption Mechanism of DHP107, Oral Paclitaxel Formulation for Single-Agent Anticancer Therapy

Paclitaxel, administered as intravenous infusion currently, is an effective anticancer drug belonging to the taxane family (Figure 1) and used in the treatment of a wide variety of cancers including breast and ovarian cancers (Rowinsky et al., 1995). Researchers have been looking for more effective and convenient ways to administer paclitaxel with less formulation-related toxicities than the commercially available formulations like Taxol® by Bristol-Meyers Squibb. It is well known that some of the limitations of the current formulation come from Cremophor EL, a polyoxyethylated castor oil. This particular component is known to cause hypersensitivity (Weiss et al., 1990), to be responsible for nonlinear pharmacokinetic behavior (Kearns et al., 1995; Gianni, 1995) and to cause paclitaxel precipitation oftentimes when diluted during the infusion process (Pfeifer, 1993). Formulations for paclitaxel and its analogs have been prepared in many different ways for various administration procedures (Kim et al., 2006; Xie et al., 2007; Sugahara et al., 2007; Singla et al., 2002; Hennenfent & Govindan, 2006). Several years ago, Abraxane®, a suspension of albumin nanoparticles containing paclitaxel, obtained approval to treat metastatic breast cancer patients (Ibrahim et al., 2002; Garber, 2004). Abraxane®, a solvent-