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Artemether has been used for a long time in the treatment of malaria as safe and non expensive drug. It possesses potent anticancer effects in cancer cell lines. Our aim was to develop transferrin-modified-artemether lipid nanospheres as targeted anticancer drug delivery system. In this study, artemether intravenous delivery system was prepared by emulsifying method as lipid nanospheres containing mixture of soya oil and crodamol as the core and soya lecithin and Tween 80 as coating layer. According to the physicochemical characterization, the process and formulation variables were optimized by orthogonal design and ANOVA analysis. Based on the electrostatic interaction, transferrin (TR) was physically adsorbed onto the coating layer; the effect of medium pH and the charge of the nanocarriers on the adsorption were investigated. The in vitro characterizations were carried out including, the zeta potential, AFM, TEM, FTIR, 1H NMR and gel filtration. ART-LNSs with high entrapment efficiency, small size of about 50 nm and monodispersity were formulated. Optimized and stable TR-LNSs, a lipoprotein like structure and size, were produced. We showed a method by which TR can be bound to lipid nanospheres without the need for chemical modification as a base for the development of safe, effective and non expensive anticancer drug delivery system.