Pharmacokinetic evaluation and antitumor activity of 2-methoxyestradiol nanosuspension

The aim of the present study was to evaluate the pharmacokinetic and antitumor activity of 2-methoxyestradiol (2-ME) nanosuspension relative to 2-ME solution both in vitro and in vivo. The pharmacokinetics of 2-ME administered either as a nanosuspension or as a solution were compared after I. V. administration to rats. In plasma, 2-ME nanosuspension exhibited a significantly (p < 0.01) reduced C-max (1022.8 +/- 467.4 ng/mL versus 2559.2 +/- 775.8 ng/mL) and AUC(0-240min) (41566.8 +/- 965.5 ng/mL min versus 79557.7 +/- 256.2 ng/mL min), and a significantly (p < 0.01) greater volume of distribution (3.18-fold), clearance (1.85-fold), and elimination half-life (156.6 +/- 33.5 min versus 70.0 +/- 22.6 min) compared to the 2-ME solution. Methyl tetrazolium (MTT) assay showed that nanosuspension could significantly enhance the cytotoxicity of 2-ME on EC9706 cells in vitro. After 72 h exposure, the IC50 value of 2-ME nanosuspension was much lower than that of 2-ME solution (1.81 +/- 0.15 mu mol/L versus 4.14 +/- 0.30 mu mol/L). Studies on BALB/c mice with EC9706 solid tumors demonstrated significantly greater inhibition of tumor growth following treatment with 2-ME nanosuspension than 2-ME solution at the same dosage. These results suggest that the delivery of 2-ME nanosuspension is a promising approach for the treatment of tumors.