5-Fluorouracil-Impregnated PLGA Coated Gold Nanoparticles for Augmented Delivery to Lung Cancer: in vitro Investigations

Abstract

Background and Objective: The study aimed to investigate the augmented cytotoxic effects of polymer-coated (poly-lactic-co-glycolic acid-PLGA) gold nanoparticles (GNPs) carrying 5-fluorouracil (5-FU) in the management of lung cancer. Materials and Methods: In this study, several formulations were prepared using a double emulsion (water-oil-water) method and evaluated for drug release behavior, compatibility, cell line toxicity (A549), and apoptosis assessment. Results: Characterization results showed spherical polydispersed particles with size 29.11-178.21 nm, polydispersity index (PDI) 0.191-292, and zeta potential (ZP) 11.19-29.21 (-mV), respectively. The optimized polymer-coated 5-FU loaded gold nanoparticles (PFGNPs) illustrated a maximum drug loading (93.09 ± 10.75%) compared to others. The percent cumulative drug release of polymer-coated 5-FU loaded nanoparticles (PFNPs), 5-FU loaded gold nanoparticles (FGNPs), (PFGNPs) and 5-FU solution were 47.87± 1.5, 41.09±1.8, 56.31±1.05, and 98.8±4.2%, respectively, over 10 h. following zero-order release kinetics (except 5-FU solution). From the MTT results, the cytotoxic effect of PFGNPs on the A549 cells was 82.89 % compared to the 5-FU solution (74.91 %). EGFR and KRAS gene expression analysis under the influence of PFNPs, FGNPs, PFGNPs, and 5-FU was studied and observed maximum potency for PFNPs. Conclusion: PLGA coated biogenic gold nanoparticles have a combined effect to achieve high drug loading, sustained delivery, improved efficacy, and enhanced permeation. Conclusively, the approach may be promising to control lung cancer with reduced toxicity and improved efficacy.