title: 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 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.
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China.
authors.forename: Shuzhang
authors.initials: S
authors.lastname: Du
authors.forename: Ling
authors.initials: L
authors.lastname: Zhu
authors.forename: Bin
authors.initials: B
authors.lastname: Du
authors.forename: Xiufang
authors.initials: X
authors.lastname: Shi
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Shuyu
authors.initials: S
authors.lastname: Wang
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000077584:2-Methoxyestradiol; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D004958:Estradiol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013535:Suspensions / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D013535:Suspensions; D004958:Estradiol; D000077584:2-Methoxyestradiol