Effect of paclitaxel content in the DHP107 oral formulation on oral bioavailability and antitumor activity

Abstract

DHP107 is a novel lipid-based oral paclitaxel formulation for the treatment of various cancers. In the present study, to increase the treatment effect of DHP107, we aimed to improve this formulation. We optimized the paclitaxel content in DHP107 formulation, evaluated its antitumor activity, and compared its activity with that of the intravenous paclitaxel formulation, Taxol？, in various mouse cancer models. The oral bioavailability of paclitaxel increased dose-dependently up to 50&#8239

mg/kg. However, the paclitaxel absorption from the DHP107 formulations containing ≥1.5% (w/v) paclitaxel decreased with the increase in DHP107 dose as paclitaxel was crystallized when exposed to water. Therefore, the optimized DHP107 formulation containing 1% (w/v) paclitaxel was selected, and it exhibited similar antitumor activity as Taxol？. However, the DHP107 showed a better survival rate with low toxicity than that of Taxol？. The concentration of paclitaxel in the tumor tissues of mice in the DHP107 was also higher than that in Taxol？. The optimized DHP107 formulation might reduce the possible toxic effects of the formulation, with antitumor activities similar to those of intravenous paclitaxel Taxol？, by enhancing the distribution to tumor tissues. Furthermore, it might be beneficial to use DHP107 for patients with hypersensitivity reactions to intravenous Taxol？.