Epigallocatechin-3-gallate\nSynergistically Inhibits\nthe Proliferation of Lung Cancer Cells with Gemcitabine by Induction\nof Apoptosis Mediated by ROS Generation

The present study focused on the formulation, characterization,\nand evaluation of solid lipid nanoparticles (SLNs) loaded with gemcitabine\n(GEM) and epigallocatechin-3-gallate (EGCG) for lung cancer treatment.\nA 2-level, 3-factor factorial design was used to optimize various\nprocess parameters in the preparation of SLNs. The average particle\nsize and polydispersity index (PDI) of GEM-EGCG SLNs were found to\nbe 122.8 ± 8.02 and 0.1738 ± 0.02, respectively. Drug loading\nand release studies indicated a sustained release behavior for GEM-EGCG\nSLNs, with release kinetics confirmed by the Higuchi model. Cell viability\nand anticancer activities were assessed using the MTT assay, which\ndetermined an IC<sub>50</sub> value of 12.5 μg/mL for GEM-EGCG\nSLNs against A549 cell lines (lung carcinoma epithelial cells). The\nSLNs were able to internalize into the nuclei of cells, likely due\nto their small particle size, and were effective in killing cancer\ncells. Additionally, a study of ROS production-mediated apoptosis\nof A549 cells was performed through FACS. GEM-EGCG SLNs were found\nto be stable for 3 months. <i>In vivo</i> studies revealed\nbetter drug distribution in the lungs and improved pharmacokinetic\nprofile compared with pure drugs. Overall, the results suggest that\ncombining GEM and EGCG in biocompatible SLNs has resulted in synergistic\nantitumor potential and improved bioavailability for both drugs, making\nit a promising anticancer therapeutic regimen against lung cancer.