Tamoxifen-2-hydroxylpropyl-β-cyclodextrin-aggregated nanoassembly for nonbreast estrogen-receptor-positive cancer therapy

Abstract

Background: Tamoxifen (Tam) is used for the treatment and prevention of estrogen-receptor-positive human breast and other cancers. Its use in ovarian cancer has not been well studied. Method: We formulated and characterized a water-soluble Tam-2-hydroxylpropyl-β-cyclodextrin (HPβCD; 1:2 M) complex. Results: The differential scanning calorimetery of Tam-HPβCD indicated the transition of Tam from crystalline to amorphous form on addition of HPβCD. ¹H-nuclear magnetic resonance nuclear overhauser effect cross-peaks between phenyl moieties of Tam and HPβCD, and downfield shifts in H-3 (0.26) and H-5 (0.29) protons of HPβCD suggested the inclusion of Tam in HPβCD cavity. Transmission-electron microscopy studies of HPβCD and the Tam-HPβCD complex revealed the formation of aggregated nanoassembly at 60-180 nm. Dimethyl thiazol diphenyltetrazolium bromide assay demonstrated 7.37 ± 2.32% cell survival of OAW-42 cells with 3 μg/ml Tam concentration. Conclusion: The Tam-HPβCD nanoassembly entered the cell owing to enhanced permeability and retention property of tumor cell and antiestrogenic Tam and, therefore, resulted in excellent anticancer efficacy in the ovarian cancer cell line.