Etoposide was incorporated in an injectable parenteral emulsion, in an attempt to alter its pharmacokinetics and improve anticancer activity. Parenteral emulsion of etoposide (EPE), which remained stable over 6 months' storage, was prepared (under optimal experimental conditions) using soybean oil and phosphatidylcholine as emulsifier. The particle size distribution and zeta potential were measured using photon correlation spectroscopy. The pharmacokinetics and tissue distribution of EPE and commercial etoposide injectable solution (ETP) were studied in Swiss albino mice. The antitumor activity was performed on BDF1 mice bearing Lewis lung carcinoma. The particle size distribution with polydispersity indices, zeta potential, entrapment efficacy, and assay of EPE were found to be 218.7 +/- 4.7 (0.14 +/- 0.0) nm, -53.5 +/- 0.2 mV, 75 +/- 2.1%, and 0.85 +/- 0.1 mg/mL, respectively. The EPE was stable for >6 months and drug leaching was 5.8 +/- 1.5%. The pharmacokinetics and tissue distribution of EPE was significantly different than that of ETP. The EPE showed high AUC(0-alpha), MRT (mean residence time), and lower clearance than that of ETP. It was found that etoposide concentration was higher in liver, spleen, and lung after ETP administration when compared with EPE; however, in heart and brain, etoposide was more after EPE than that of ETP. The EPE showed lower reticuloendothelial system (liver and spleen) tissue uptake. The anticancer activity of EPE was higher in Lewis lung carcinoma-bearing mice. On the fifteenth day of transplantation, the percentage of tumor growth suppression rate was 63.23% in EPE-treated mice and 33.78% in ETP-treated mice.
Copyright 2004 Wiley-Liss, Inc.