Characterization and evaluation of nanostructured lipid carrier as a vehicle for oral delivery of etoposide

Nanostructured lipid carriers (NLCs) are a new generation of lipid nanoparticles, which have showed some advantages over traditional lipid nanoparticles, such as improved drug incorporation and release properties. The purpose of this study is to develop an optimized nanostructured lipid carrier formulation for etoposide (VP16), and to estimate the potential of NLCs as oral delivery system. VP16-NLCs were prepared by an emulsification and low-temperature solidification method. The average drug entrapment efficiency, particle size and zeta potential of VP16-NLCs, VP16-PEG40-St-modified NLCs (VP16-PEG40-NLCs) and VP16-DSPE-PE- modified NLCs (VP16-DSPE-NLCs) were 57.9-89.7%, 125.9-91.2 nm and -28.49 to -15.34 mV, respectively. The absorption of VP16-NLCs in the intestine was performed by the diffusion chamber. It was found that VP16-DSPE-NLCs with a smaller particle size made the drug transport easy from mucosal to serosal side. A pharmacokinetic study was conducted in rats. After oral administration of VP16 at a dose of 180 mg/kg in the form of either VP16-NLCs or suspension, the relative bioavailability of VP16-NLCs, VP16-PEG40-NLCs and VP16-DSPE-NLCs were enhanced about 1.8-, 3.0- and 3.5-fold, respectively, compared with VP16 suspension. Furthermore, VP16-DSPE-NLCs displayed the highest cytotoxicity against human epithelial-like lung carcinoma cells. The NLCs formulation remarkably improved the oral bioavailability of VP16 and demonstrated a promising perspective for oral delivery of VP16.