Pharmacokinetic evaluation and antitumor activity of 2-methoxyestradiol nanosuspension

Abstract

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 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.

Keywords::

• 2-Methoxyestradiol
• nanosuspension
• pharmacokinetics
• cytotoxicity
• antitumor

Acknowledgment

We thank Dr. Xiufang Shi for providing the material of 2-ME. We also thank Dr. Zhengquan Zhang for helpful proposition.

Declaration of interest

This work was financed supported by the Technology Innovation Talents Program Foundation of Henan Province, No. 094200510002.