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

Gautam Chauhan; Xuechun Wang; Carol Yousry; Vivek Gupta

doi:10.3390/pharmaceutics15030996

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

Pharmaceutics. 2023 Mar 20;15(3):996. doi: 10.3390/pharmaceutics15030996.

Authors

Gautam Chauhan¹, Xuechun Wang¹, Carol Yousry^{1

2}, Vivek Gupta¹

Affiliations

¹ Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.
² Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini, Cairo 11562, Egypt.

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.

Keywords: hot melt extrusion; lung delivery; nanoemulsion; nanorepurposing; non-small cell lung cancer; scalability; super-refined excipients.

Grants and funding

This project was funded with the research funds to Vivek Gupta by the College of Pharmacy and Health Sciences, St. John’s University, Queens, NY. Gautam Chauhan and Xuechun Wang were supported by the teaching assistantships of St. John’s University. Carol Yousry was supported by a US-Egypt Higher Education Initiative Graduate Scholarship from USAID.