Enhanced Codelivery of Gefitinib and Azacitidine for Treatment of Metastatic-Resistant Lung Cancer Using Biodegradable Lipid Nanoparticles

Abstract

Lung cancer is a formidable challenge in clinical practice owing to its metastatic nature and resistance to conventional treatments. The codelivery of anticancer agents offers a potential solution to overcome resistance and minimize systemic toxicity. The encapsulation of these agents within nanostructured lipid carriers (NLCs) provides a promising strategy to enhance lymphatic delivery and reduce the risk of relapse. This study aimed to develop an NLC formulation loaded with Gefitinib and Azacitidine (GEF-AZT-NLC) for the treatment of metastatic-resistant lung cancer. The physicochemical properties of the formulations were characterized, and in vitro drug release was evaluated using the dialysis bag method. The cytotoxic activity of the GEF-AZT-NLC formulations was assessed on a lung cancer cell line, and hemocompatibility was evaluated using suspended red blood cells. The prepared formulations exhibited nanoscale size (235–272 nm) and negative zeta potential values (−15 to −31 mV). In vitro study revealed that the GEF-AZT-NLC formulation retained more than 20% and 60% of GEF and AZT, respectively, at the end of the experiment. Hemocompatibility study demonstrated the safety of the formulation for therapeutic use, while cytotoxicity studies suggested that the encapsulation of both anticancer agents within NLCs could be advantageous in treating resistant cancer cells. In conclusion, the GEF-AZT-NLC formulation developed in this study holds promise as a potential therapeutic tool for treating metastatic-resistant lung cancer.

Lipid Nanoparticles in Lung Cancer Therapy

“…The comprehensive characterization of these nanoparticles included physicochemical properties, drug release, cytotoxic activity, and hemocompatibility evaluation. The results showed promise in treating resistant lung cancer cells while demonstrating hemocompatibility and safety, indicating their potential effectiveness in clinical settings [39].…”

“…Lung Cancer [29] Transferrin-conjugated lipid-coated poly(D,L-lactic-co-glycolic acid) nanoparticles Doxorubicin Targeted Therapy for Lung Cancer [30] Core-shell-type lipid-polymer hybrid nanoparticles composed of hydrogenated soy phosphatidylcholine and 1,2-distearoyl-snglycero- Biodegradable lipid nanoparticles (NLC) Gefitinib and Azacitidine Co-delivery for Treatment of Metastatic-Resistant Lung Cancer [39] Lipid-Polymer Hybrid Nanoparticles using Poly(lactic-co-glycolic acid) (PLGA), Poly(caprolactone) (PCL), Soy Phosphatidylcholine, and 1,2-Distearoyl-snglycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] (DSPE-PEG)…”

“…Particle size can be measured using techniques like dynamic light scattering (DLS) or nanoparticle tracking analysis (NTA), with the optimal range typically being 50-200 nm to exploit the enhanced permeability and retention (EPR) effect for tumor targeting. The zeta potential, indicating the surface charge of LNPs, can be assessed through electrophoretic light scattering, offering insights into their stability and interaction with biological membranes [16,19,26,39].…”

“…Techniques such as confocal microscopy provide a detailed visualization of the cellular internalization and intracellular localization of fluorescently labeled LNPs. Flow cytometry quantifies the uptake of LNPs by measuring fluorescence intensity, and fluorescence microscopy is employed to observe and quantify the internalization of these particles [26,39].…”

“…The strategic formulation of LNPs, such as EGF conjugated hybrids and PEGylated nanostructured carriers, have shown reduced systemic toxicity and enhanced tumor-specific activity [20,23,30,33,38,39,88,92].…”