Evaluating Cytotoxicity of Hyaluronate Targeted Solid Lipid Nanoparticles of Etoposide on SK-OV-3 Cells

The epithelial ovarian carcinoma is one of the most fatal gynecological cancers. Etoposide is used in treating platinum-resistant ovarian cancer. Sodium hyaluronate is a substance that binds to the CD44 receptors overexpressed in SK-OV-3 cells of epithelial ovarian carcinoma. The aim of the present work was to study the cytotoxicity effect of hyaluronate targeted solid lipid nanoparticles (SLNs) of etoposide on SK-OV-3 cells. The cytotoxicity of the targeted and nontargeted SLNs of etoposide was compared to free drug on the SK-OV-3 cells by MTT assay method. The cellular uptake of the targeted and nontargeted nanoparticles containing sodium fluorescein was also studied. The difference of cell vitality between nontargeted nanoparticles and also targeted nanoparticles with free drug was significant. Targeted nanoparticles also caused more toxicity than nontargeted nanoparticles ( ). After 4 hours of incubating, the fluorescence was remarkably higher in the cells treated by targeted SLNs rather than nontargeted ones, and there was no observable fluorescence in cells incubated with pure sodium fluorescein. Hyaluronate targeted SLNs containing etoposide increased the cytotoxicity of etoposide on SK-OV-3 cells which may be a worthwhile potential method for reducing the prescribed dose and systemic side effects of this drug in epithelial ovarian carcinoma. 1. Introduction The epithelial ovarian carcinoma is one of the most fatal gynecological cancers across the globe. In spite of early recovery by surgical and chemotherapy treatments, the 5-year survival rate for the patients is only 13 percent. The database GLOBCAN related to the World Health Organization (WHO) has reported incidence of about 192000 cases in the world, in the year of 2000. 6000 cases of the mentioned cases have occurred in the UK, and 21000 cases in the U.S. For treating the disease, the tumor will be removed by surgical procedures and then chemotherapy would be started with platinum-based chemotherapy (cisplatin and carboplatin), which treating regime includes cisplatin and carboplatin with the drugs such as paclitaxel, docetaxel, cyclophosphamide, and doxorubicin. In some of the patients, the disease relapses after 6 months of chemotherapy; this condition is defined as platinum resistant, in which treatment would be continued with drugs such as topotecan and etoposide [1]. Etoposide, as other chemotherapy agents, has many side effects such as bone marrow suppression, granulocytopenia, thrombocytopenia [2], mucositis, moderate to severe esophagitis, hepatotoxicity, metabolic acidosis, and