The aim of the present study was preparation of hyaluronan (HA) targeted solid lipid nanoparticles (SLNs) of etoposide. SLNs were prepared by an emulsification-solvent evaporation method and physically coated with HA. Four variables, including the ratio of cetyl alcohol to cationic lipid, cationic lipid type (stearylamine (SA) or dodecylamine (DDA)), lipid to HA ratio, and organic to aqueous phase ratio, were studied in an irregular fraction factorial design. Four responses, including particle size, zeta potential, drug loading, and 24-hour release efficiency percent, were measured for each formulation and then the optimization was carried out. The percent of HA coated on the SLNs was calculated by CHN elemental analysis which was shown to be about 55.89%. The cationic lipid type and the ratio of cetyl alcohol to cationic lipid had the highest influence on particle size and zeta potential, respectively. The highest effects of the ratio of lipid to HA and the organic to aqueous phase ratio were on the drug loading efficiency of SLNs. The optimized formulation of SLNs was obtained by SA, the equal proportion of cetyl alcohol and cationic lipid, the ratio of 1.5 for lipid to HA, and 10% of organic phase to aqueous phase.
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 (P < 0.05). 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.
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