The preparation, characterization of vincristine and ε-viniferine loaded polymeric nanoparticles and in vitro applications of these nanoparticles on the targeting cancer treatment

The studies are focused on the targeting of the drug by loading it in the carrier system because of biodistribution, the requirement of high dose, the state of low affinity in the pathological regions and toxic effects of conventional chemotherapy drugs. Vincristine Sulfate (VS) is commonly used in chemotherapy and is a specific anti-cancer agent against cell-cycle. Previously, it has been shown that the combine use of EV and VS has a synergistic effect on HepG2 cells. The aim of this thesis, the preparation of EV and VS loaded PLGA-b-PEG nanoparticle formulation that can provide passive targeting in order to reduce the adverse effects due to high doses of VS. The particle size, zeta potential and polydispersity index of the formulation prepared by nanoprecipitation method were determined. Atomic Force Microscopy (AFM) results showed that nanoparticles have a spherical shape and smooth surface features. In vitro release studies and thermal analysis were performed in pH 7.4 Tris-HCl buffer and by Differential Scanning Calorimetry (DSC), respectively. The rate of influx of coumarin-6 labelled nanoparticles into HepG2 cells was investigated by either qualitative or quantitative analysis after various of time points. It was appropriate for cellular uptake. The results obtained from MTT assay showed that drug loaded PLGA-b-PEG nanoparticles are highly effective on HepG2 cell viability than free forms of the drug. The rate of apoptosis was determined by Acridine orange/Propidium iodide staining and Annexin V-FITC flow cytometry analysis. Consequently, using EV and VS loaded PLGA-b-PEG nanoparticles with passive targeting is enhanced uptake and efficacy of cytotoxic effects in HepG2 cells that might reduce the side effects of VS and improve patient quality of life.