Conventional, stealth and transferrin-conjugated liposomes for artemisinin delivery to cancer cells

Artemisinin is a sesquiterpene lactone isolated from Artemisia annua having an unusual endoperoxyl moiety which is essential for the activity when activated by iron [1]. In addition to its well established antimalarial properties artemisinin has potent anticancer activities in a variety of human cancer cell types [2]. The cytotoxic effect of artemisinin is specific to cancer cells because transferrin-receptors are highly expressed on the surfaces of tumour cells and iron content is higher than in normal cells [3]. The aim of our work was to develop conventional and stealth liposomes for passive targeting and transferrin-conjugated liposomes for active targeting loaded with artemisinin. Multilamellar vesicles were prepared according to the film hydratation method; in order to reduce the dimensions of the vesicles, an high pressure homogenizer Emulsiflex C3® was used. Conventional, stealth and targeted liposomes were fully characterized by particle size, zeta potential, PdI, drug entrapment efficiency and transmission electron microscopy. Coupling of transferrin to the targeted liposomes was obtained by amide bound between Tf and lipid linker and the average amount of transferrin conjugated to the liposome was quantified with bicinchonic acid (BCA). A preliminary study about the cellular uptake of conventional liposomes loaded with fluorescein sodium salt has been performed in K562 cells using flow cytometry analysis and fluorescence microscopy; the highest internalization of fluorescein sodium salt loaded liposomes was after 60 minutes of exposure.

References: 1. Nakase I et al. (2008) Int J Pharm 354: 28–33.

2. Firestone GL et al. (2009) Expert Rev Mol Med 11: e32.

3. Efferth T et al. (2004) Free Radic Biol Med 37: 998–1009.