Diclofenac Sodium and Gentamicin Co-Encapsulated PLGA Nanoparticles: Targeting Extracellular Matrix Components to Combat Biofilm Formation in Pseudomonas aeruginosa PAO1

Non-steroidal anti-inflammatory drugs (NSAIDs) have received attention to be used in combination with antibiotics in antibacterial chemotherapy. However, this study is the first to explore the impact of dual encapsulation of diclofenac sodium and gentamicin within PLGA nanoparticles (DS-GEN-PLGA NPs) on inhibiting extracellular matrix components and biofilm eradication of Pseudomonas aeruginosa PAO1. DS-GEN-PLGA NPs were prepared using the double emulsion solvent evaporation (DESE) technique and characterized by various characterization techniques. Subsequently, the inhibition and eradication potential of DS-GEN-PLGA NPs against P. aeruginosa biofilm was explored. The DS-GEN-PLGA NPs are spherical and oval and 80–200 nm in diameter. DS-GEN-PLGA NPs significantly reduced biofilm formation by 76.28%, biofilm metabolic level by 69.8%, biofilm exopolysaccharide by 75.3%, alginate production by 32.56%, and eDNA release by 60.2%. The expression level of the lasI and rhlI decreased by 0.29 and 0.44 folds compared with untreated cells. This study indicates that DS-GEN-PLGA NPs have promising antibiofilm activity against P. aeruginosa, highlighting its potential as a novel therapeutic formulation to combat biofilm-related infections.