Human serum albumin nanoparticulate system with encapsulation of gefitinib for enhanced anti-tumor effects in non-small cell lung cancer

Gefitinib, a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has showed remarkable activity in non-small cell lung cancer patients with tumors carrying sensitive EGFR mutation. However, Iressa (R) tablets present problems, including insolubility, large absorption disparity, low oral bioavailability, gastrointestinal side effects and drug resistance, which limit their application. In present study, we developed gefitinib-loaded human serum albumin nanoparticles (GFNPs) by Nab (TM) technology for intravenous administration. By utilizing oleic acid as a co-emulsifier, which could increase the binding of gefitinib to human serum albumin, GFNPs were successfully fabricated with an amorphous state in GFNPs and its release from the nanoparticles conformed to the Ritger-Peppas process. The albumin nanoparticles could rapidly disassociate in the bloodstream and were effectively uptaken by the NCI-H358 cells via the mechanisms of secreted protein acidic and rich in cysteine (SPARC)-mediated transport, resulting in higher growth inhibition and apoptosis induction compared to free gefitinib. In tumor-bearing mice, the albumin nanoparticles demonstrated an increased, lasting tumor distribution. Compared with the commercial Iressa, GFNPs at only 10% of Iressa dose showed superior antitumor efficacy, with little effect on body weight of mice, suggesting that GFNPs might serve as a clinical candidate for a safe and effective anti-non-small cell lung cancer treatment.