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.

Decoding dynamic interactions between EGFR‐TKD and DAC through computational and experimental approaches: A novel breakthrough in lung melanoma treatment

“…On evaluating the effect against the Hop‐6 cell line, the IC 50 value for CTX‐1 was found to be 8.5 ± 1.2 μM, compared with erlotinib, which displayed an IC 50 value of 7.3 ± 0.5 μM. These findings provide intriguing insights into the inhibitory potency of CTX‐1 and erlotinib against these specific cancer cell lines 37,38 …”

“…These findings provide intriguing insights into the inhibitory potency of CTX‐1 and erlotinib against these specific cancer cell lines. 37 , 38 …”

A novel therapeutic outlook: Classification, applications and challenges of inhalable micron/nanoparticle drug delivery systems in lung cancer (Review)

“…NEs, through efficient enhancement of gambogic acid solubility, and the CS-siRNA complexation via electrostatic interactions, achieve improved siRNA protection and rapid drug release upon intracellular entry through a pH-responsive proton sponge effect, facilitating enhanced therapeutic efficacy. By contrast, Chauhan et al ( 62 ) optimized and evaluated the physicochemical properties and aerosol deposition behavior of prepared NEs. Using hot melt extrusion technology, NEs loaded with tyrosine kinase inhibitors and erlotinib were successfully manufactured in a single-step, continuous process without the need for additional size reduction steps, thereby facilitating scalability and enabling efficient aerosol deposition in deep lung regions ( 62 ).…”

“…By contrast, Chauhan et al ( 62 ) optimized and evaluated the physicochemical properties and aerosol deposition behavior of prepared NEs. Using hot melt extrusion technology, NEs loaded with tyrosine kinase inhibitors and erlotinib were successfully manufactured in a single-step, continuous process without the need for additional size reduction steps, thereby facilitating scalability and enabling efficient aerosol deposition in deep lung regions ( 62 ). Furthermore, Asmawi et al ( 60 ) employed response surface methodology based on central composite design to optimize the preparation conditions of NEs with the desired particle size.…”

Three-Dimensional In Vitro Tumor Spheroid Models for Evaluation of Anticancer Therapy: Recent Updates

“…Chauhan et al [44] investigated the in vitro efficacy of inhaled erlotinib nanoemulsion in the NSCLC A549 cell line.…”