Non-small cell lung cancer-targeted, redox-sensitive lipid-polymer hybrid nanoparticles for the delivery of a second-generation irreversible epidermal growth factor inhibitor—Afatinib: In vitro and in vivo evaluation

Abstract

Afatinib (Afa), a second-generation irreversible epidermal growth factor inhibitor for the development of non-small cell lung cancer, has low bioavailability and adverse reactions. Nanoscaled drug delivery systems offer promising alternatives to address these defects and improve therapeutic outcomes. In the present study, a Tf contained, redox-sensitive ligand was synthesized and used for the preparation of afatinib loaded, Tf modified redox-sensitive lipid-polymer hybrid nanoparticles (Tf-SS-Afa-LPNs). Subsequently, studies of biological experiments in vitro and in vivo were performed to investigate the therapeutic effect of the system in lung cancer. The results showed that Tf-SS-Afa-LPNs has particle size of 103.5 ± 4.1 nm and zeta potential of -21.2 ± 2.4 mV. Significantly higher drug release was observed in the presence of glutathione (GSH). The area under the plasma concentration – time curve (AUC), peak concentration (Cmax) and terminal half life (T1/2) of Tf-SS-Afa-LPNs were 866.56 mg/L.h, 25.62 ± 3.21 L/kg/h, and 43.25 ± 2.31 h. Tf-SS-Afa-LPNs exhibited the most remarkable in vivo anti-tumor efficiency efficacy, which inhibited the tumor volume from 919 mm3 to 212 mm3. Tf-SS-Afa-LPNs is a promising platform for the lung cancer treatment.