Preparation, characterization and in vitro cytotoxicity of paclitaxel-loaded sterically stabilized solid lipid nanoparticles

Abstract

In an effort to develop an alternative formulation of paclitaxel suitable for parenteral administration, paclitaxel-loaded sterically stabilized solid lipid nanoparticles (SLNs) were prepared, characterized and examined for in vitro cytotoxicity. The SLNs, comprising trimyristin (TM) as a solid lipid core and egg phosphatidylcholine and pegylated phospholipid as stabilizers, were prepared using a hot homogenization method. Regardless of paclitaxel loading, the particle sizes and zeta potentials of the prepared SLNs were around 200 nm and −38 mV, respectively, suggesting that they would be suitable as a parenteral formulation. Cryo-scanning electron microscopy showed that the SLNs were homogeneous and spherical in shape, while differential scanning calorimetry measurement of the melting peak revealed that the TM exists as a solid in our formulation. Paclitaxel was loaded to the solid cores at a w/w ratio of 6%. Gel column chromatography showed that paclitaxel co-eluted with the phospholipids, indicating that paclitaxel was incorporated in the SLNs. An in vitro drug release study showed that paclitaxel was released from the SLNs in a slow but time-dependent manner. Furthermore, treatment of the OVCAR-3 human ovarian cancer cell line and the MCF-7 breast cancer cell line with paclitaxel-loaded SLNs yielded cytotoxicities comparable to those of a commercially available Cremophor EL-based paclitaxel formulation. These results collectively suggest that our optimized SLN formulation may have a potential as alternative delivery system for parenteral administration of paclitaxel.