Improved anticancer effect of L-778,123, a Farnesyl-transferase inhibitor: Use of PEGylated Fe3O4 nanoparticles

Abstract

L-778,123 is a Farnesyl-transferase inhibitor and a potent anticancer agent. However, the development of this compound was discontinued because of severe cytotoxicity i. e. thrombocytopenia and neutropenia. The aim of this study was to decrease the adverse side effects of L-778,123 by using PEGylated Fe<inf>3</inf>O<inf>4</inf> nanoparticles. L-778,123 (an imidazole-containing FTase inhibitor) as an anticancer agent was encapsulated by prepared PEGylated Fe<inf>3</inf>O<inf>4</inf> nanoparticles. Nanoparticles were characterized using vibrating sample magnetometer (VSM), transmission electron microscopy (TEM), X-ray diffractometry (XRD) and Fourier transform infrared spectroscopy (FT-IR) methods. The encapsulation efficiency, release profile and cytotoxicity of free L-778,123 and L-778,123-loaded magnetic nanoparticles were evaluated in vitro using human colon (HT-29) and lung (A549) cancer cell lines by MTT assay. The encapsulation efficiency of prepared PEG modified Fe<inf>3</inf>O<inf>4</inf> magnetic nanoparticles of L-778,123 was about 70%. The release of L-778,123 from magnetic nanoparticles showed a three phasic profile. The half maximal inhibitory concentration (IC<inf>50</inf>) of L-778,123-loaded magnetic nanoparticles was significantly higher than free L-778,123 which is related to sustained drug release profiles. The PEG coated magnetic nanoparticles showed low cytotoxicity which is ideal for biomedical applications. é ECV آ· Editio Cantor Verlag, Aulendorf (Germany).