Drug Design, Development and Therapy (Dec 2017)
Redox-responsive and pH-sensitive nanoparticles enhanced stability and anticancer ability of erlotinib to treat lung cancer in vivo
Abstract
Sheng Tan, Guoxiang Wang Department of Thoracic Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China Purpose: Erlotinib (ETB) is a well-established therapeutic for non-small-cell lung cancer (NSCLC). To overcome drug resistance and severe toxicities in the clinical application, redox-responsive and pH-sensitive nanoparticle drug delivery systems were designed for the encapsulation of ETB. Methods: Poly(acrylic acid)-cystamine-oleic acid (PAA-ss-OA) was synthesized. PAA-ss-OA-modified ETB-loaded lipid nanoparticles (PAA-ETB-NPs) were prepared using the emulsification and solvent evaporation method. The tumor inhibition efficacy of PAA-ETB-NPs was compared with that of ETB-loaded lipid nanoparticles (ETB-NPs) and free ETB anticancer drugs in tumor-bearing mice. Results: PAA-ETB-NPs had a size of 170 nm, with a zeta potential of -32 mV. The encapsulation efficiency and drug loading capacity of PAA-ETB-NPs were over 85% and 2.6%, respectively. In vitro cytotoxicity of ETB-NPs were higher than that of ETB solution. The cytotoxicity of PAA-ETB-NPs was the highest. The in vivo tumor growth inhibition by PAA-ETB-NP treatment was significantly higher than that by ETB-NPs and ETB solution. No obvious weight loss was observed in any of the treatment groups, indicating that all the treatments were well tolerated. Conclusion: PAA-ETB-NPs could enhance the stability and anti-cancer ability of ETB to treat lung cancer and are a promising drug delivery system for lung cancer treatment. Keywords: epidermal growth factor receptor, kinase inhibitor, pH-sensitive, redox-responsive, poly(acrylic acid)
