Publication

Abstract : Breast cancer (BC) is the most prevalent cancer in women. Raloxifene (RLX), a selective estrogen receptor modulator has been investigated for the treatment of uterine and BC. However, the major drawbacks of RLX are low water solubility (345.2 ± 15.6 μg/mL), extensive gut metabolism (>90 %) and poor oral bioavailability (<2 %). Hence, physicochemical and biopharmaceutical features of RLX cause hindrance for oral delivery in the treatment of BC. Therefore, we have developed raloxifene loaded d-α-tocopheryl polyethylene glycol succinate-stabilized poly (ε-caprolactone) nanoparticles (RNP) to offer sustained release through parenteral route of administration in the treatment of BC. The RNP post optimization with Box-Behnken design (BBD) demonstrated particle size of 120 ± 1.127 nm with PDI (Polydispersity index) of 0.122 ± 0.014. Further, infrared spectroscopy displayed absence of any chemical interaction. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) highlighted successful amorphization of the RLX. RLX exhibited an IC50 value of 23.17 ± 2.58-μM insignificantly (Unpaired t-test, P < 0.05) different from IC50 value of 20.07 ± 3.16 μM of RNP in standard cell proliferation assay carried out on MCF-7 cells. Cell uptake studies demonstrated successful internalization of RNP in MCF-7 cells preferably through endocytosis pathway. On the other hand, cell cycle analysis verified that 49.53 ± 0.22 % MCF-7 cells were found in the G0/G1 cells that increased to 79.63 ± 0.42 % and 87.69 ± 0.22 %, respectively after 24 h of treatments with RLX and RNP. The increment in apoptotic cell death may be credited to intracellular localization of high population of RNP. These results suggested that the anti-proliferative activity of RNP in MCF-7 cells might be partly caused by G0/G1 phase cell arrest. In conclusion, RNP dispersion warrants further investigation in xenograft model of BC for translating in to a clinically viable product.