Solid lipid nanoparticles of temozolomide: Potential reduction of cardial and nephric toxicity

The aim of this study was to prepare temozolomide solid lipid nanoparticles (TMZ-SLNs), to evaluate its physiochemical characteristics, and to investigate the specific drug targeting of intravenous (i.v.) injected solid lipid nanoparticles of temozolomide. TMZ-SLNs was prepared by an emulsification and low-temperature solidification method. In vitro drug release was conducted in phosphate-buffered saline (pH 6.8) at 37 °C. The concentrations of the temozolomide in selected organs were determined using reversed-phase high-performance liquid chromatography (HPLC) following i.v. administration of the TMZ-SLNs and a temozolomide solution (TMZ-Sol). The results show that the TMZ-SLNs had an average diameter of 65.9 ± 11.8 nm with a zeta potential of −37.2 ± 3.6 mV and the in vitro drug release was monitored for up to 3 days, and the release behavior was in accordance with Higuchi-equation. In the tested organs, the AUC/dose and the mean residence times (MRT) of the TMZ-SLNs were much higher and longer than those of the TMZ-Sol, especially in brain and reticuloendothelial cells-containing organs. The AUC ratio of TMZ-SLNs to TMZ-Sol in the brain was the highest among the organs. These results indicated that the SLNs is a promising sustained-release and drug-targeting system for antitumor drugs. It may also allow a reduction in dosage and a decrease in systemic toxicity.