Physiochemical characterization and radiolabeling of tamoxifen-cyclodextrin complex for breast cancer therapy

Objectives Breast cancer is the most common cancer in women. Tamoxifen (TAM) is a gold standard for potential use for the treatment of all stages & prevention of human breast cancer. TAM behaves like an estrogen agonist in breast & an antagonist on endometrium, bone and lipids. Side effects including proliferative effect on the endometrium, liver cancer etc are reported to be dose-dependent suggesting the use of lower doses of TAM. TAM is slightly soluble in water that requires high dosage for optimum blood concentration. A water soluble inclusion complex of cyclodextrin (HPBCD)-TAM was prepared, characterized & radiolabeled.

Methods TAM& HPBCD (1:1 molar ratio) was dissolved in water filtered & lyophilized. The complex was characterized by Differential Scanning Calorimetry (DSC) and 1-D& 2-D ¹H NMR). Cytotoxicity was assessed on MCF-7 cell line. TAM:β-HPCD was radiolabeled with Tc-99m. Radiolabled complex was injected in albino wistar rats to observed in vivo distribution.

Results An endothermic peak at 149.54^oC of TAM was disappeared in the DSC of TAM:HPBCD indicated the formation of inclusion compound of TAM:β-HPCD. Chemical shift in ¹HNMR of TAM+β-HPCD & interaction of molecules of Tamoxifen & β-HPCD (COSEY,ROSEY,TOCSY) demonstrated the formation of inclusion complex. Anticancer efficacy of complex on MCF-7 cells was significantly high. Biodistribution studies of radiolabeled TAM:β-HPCD showed renal clearance.

Conclusions TAM-HPBCD demonstrated high cytotoxicity, renal excretion & provides increased bioavailability