Preparation and characterization of Tamoxifen citrate loaded nanoparticles for breast cancer therapy

BACKGROUND Four formulations of Tamoxifen citrate loaded polylactide-co-glycolide (PLGA) based nanoparticles (TNPs) were developed and characterized. Their internalization by Michigan Cancer Foundation-7 (MCF-7) breast cancer cells was also investigated. METHODS Nanoparticles were prepared by a multiple emulsion solvent evaporation method. Then the following studies were carried out: drug-excipients interaction using Fourier transform infrared spectroscopy (FTIR), surface morphology by field emission scanning electron microscopy (FESEM), zeta potential and size distribution using a Zetasizer Nano ZS90 and particle size analyzer, and in vitro drug release. In vitro cellular uptake of nanoparticles was assessed by confocal microscopy and their cell viability (%) was studied. RESULTS No chemical interaction was observed between the drug and the selected excipients. TNPs had a smooth surface, and a nanosize range (250-380 nm) with a negative surface charge. Drug loadings of the prepared particles were 1.5%±0.02% weight/weight (w/w), 2.68%±0.5% w/w, 4.09%±0.2% w/w, 27.16%±2.08% w/w for NP1-NP4, respectively. A sustained drug release pattern from the nanoparticles was observed for the entire period of study, ie, up to 60 days. Further, nanoparticles were internalized well by the MCF-7 breast cancer cells on a concentration dependent manner and were present in the cytoplasm. The nucleus was free from nanoparticle entry. Drug loaded nanoparticles were found to be more cytotoxic than the free drug. CONCLUSION TNPs (NP4) showed the highest drug loading, released the drug in a sustained manner for a prolonged period of time and were taken up well by the MCF-7 breast cancer cell line in vitro. Thus the formulation may be suitable for breast cancer treatment due to the good permeation of the formulation into the breast cancer cells.