Scalable Production and In Vitro Efficacy of Inhaled Erlotinib Nanoemulsion for Enhanced Efficacy in Non-Small Cell Lung Cancer (NSCLC).

Abstract

Non-small cell lung cancer (NSCLC) is a global concern as one of the leading causes of cancer deaths. The treatment options for NSCLC are limited to systemic chemotherapy, administered either orally or intravenously, with no local chemotherapies to target NSCLC. In this study, we have prepared nanoemulsions of tyrosine kinase inhibitor (TKI), erlotinib, using the single step, continuous manufacturing, and easily scalable hot melt extrusion (HME) technique without additional size reduction step. The formulated nanoemulsions were optimized and evaluated for their physiochemical properties, in vitro aerosol deposition behavior, and therapeutic activity against NSCLC cell lines both in vitro and ex vivo. The optimized nanoemulsion showed suitable aerosolization characteristics for deep lung deposition. The in vitro anti-cancer activity was tested against the NSCLC A549 cell line which exhibited 2.8-fold lower IC50 for erlotinib-loaded nanoemulsion, as compared to erlotinib-free solution. Furthermore, ex vivo studies using a 3D spheroid model also revealed higher efficacy of erlotinib-loaded nanoemulsion against NSCLC. Hence, inhalable nanoemulsion can be considered as a potential therapeutic approach for the local lung delivery of erlotinib to NSCLC.