In vivo antitumor effect of endostatin-loaded chitosan nanoparticles combined with paclitaxel on Lewis lung carcinoma

Abstract

The purpose of this study was to prepare endostatin-loaded chitosan nanoparticles (ES-NPs) and evaluate their antitumor effect when combined with paclitaxel (PTX) on Lewis lung carcinoma (LLC) mouse xenografts. ES-NPs were prepared by ionic cross-linking. Characterization of the ES-NPs included size distribution, drug-loading efficiency (DL), and encapsulation efficiency (EE). An in vitro release test was also used to determine the release behavior of the ES-NPs. A subcutaneous LC xenograft model of C57BL/6J mice was established. The mice were randomly divided into six groups: control (0.9% NaCl), ES, PTX, ES-NPs, ES + PTX, and ES-NPs + PTX. The tumor volume was dynamically measured for the duration of the experiment. Immunohistochemistry was performed to determine the Ki-67 and microvascular density (MVD) in each group. Serum vascular endothelial growth factor (VEGF) and ES levels were determined by enzyme-linked immunosorbent assay (ELISA). ES-NPs were successfully synthesized and had suitable size distribution and high EE. The NPs were homogenously spherical and exhibited an ideal release profile in vitro. In vivo, tumor growth was significantly inhibited in the ES-NPs + PTX group. The tumor inhibitory rate was significantly higher in the ES-NPs + PTX group than in the other groups (p < .05). The results of the immunohistochemical assay and ELISA confirmed that ES-NPs combined with PTX had a strong antiangiogenic effect. ES-NPs can overcome the shortcomings of free ES, such as short retention time in circulation, which enhances the antitumor effect of ES. The antitumor effect was more pronounced when treatment included PTX and ES-loaded NPs.

Keywords

• endostatin
• nanoparticles
• chitosan
• paclitaxel
• lung cancer