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 IC(50) value of
2-ME nanosuspension was much lower than that of
2-ME solution (1.81 ± 0.15 μmol/L versus 4.14 ± 0.30 μmol/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.