PEGylated polypeptide lipid nanocapsules to enhance the anticancer efficacy of erlotinib in non-small cell lung cancer

Abstract

In this study, a core-shell type polypeptide-based lipid nanocapsule was developed to enhance anticancer efficacy of erlotinib in non-small cell lung cancers. Mean particle size of PEGylated polypeptide-lipid nanocapsules (PLN) for erlotinib (ERL) delivery was similar to 200 nm with an effective surface charge of -20 mV. Protective PEGylated polypeptide layer acted as a molecular fence and effectively controlled the diffusion of erlotinib from the lipid nanocapsule core, whereas pH-responsiveness of poly(L-aspartic acid) accelerated the release of erlotinib in acidic conditions. Blank lipid nanocapsules showed excellent bio-compatibility. ERL-loaded PLN (ERL-PLN) showed dose-dependent cytotoxicity in NCl-H358 and HCC-827 lung cancer cells. ERL-PLN treatment resulted in a superior tumor regression profile in a xenograft tumor model, compared to free ERL and control, suggesting high therapeutic efficacy. ERL-PLN-treated mice showed 5- and 2-fold smaller tumor volume compared to control and free ERL groups, respectively. Based on these results, PLN provide a promising drug delivery approach for lung cancer therapy. (C) 2016 Elsevier B.V. All rights reserved.