Abstract
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.
Highlights
Etoposide (VP-16) is a hydrophobic anticancer agent inhibiting topoisomerase II
Etoposide is used in the treatment of ovarian cancer [1], small cell carcinoma [2], non-Hodgkin’s lymphoma [3], Hodgkin’s lymphoma [4], and acute myelogenous lymphoma [5], with or without other drugs
It is observed that solid lipid nanoparticles (SLNs) produced from SA had smaller particle size than DDA containing ones (Figure 2)
Summary
Etoposide (VP-16) is a hydrophobic anticancer agent inhibiting topoisomerase II. despite its appropriate solubilization in vehicle solvents, its poor bioavailability concurs to disappointing results requiring the development of new delivery system forms. Etoposide is used in the treatment of ovarian cancer [1], small cell carcinoma [2], non-Hodgkin’s lymphoma [3], Hodgkin’s lymphoma [4], and acute myelogenous lymphoma [5], with or without other drugs. This drug as other chemotherapy agents has many side effects such as bone marrow suppression, granulocytopenia, thrombocytopenia [6], and gastrointestinal toxicity such as nausea, vomiting, diarrhea, mucositis, moderate to severe esophagitis, hepatotoxicity accompanied by increase in bilirubin and hepatic enzymes, metabolic acidosis, and anemia [7]. This phenomenon owes to more ratios of endocytosis in cancerous cells than healthy cells
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