Diclofenac Sodium‐Encapsulated Poly(lactic‐co‐glycolic acid) Nanoparticles: A Non‐antibiotic Formulation to Attenuate the Proteolytic Activity of P. aeruginosa Clinical Isolates

Abstract

Encapsulating drugs in poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles can provide a gradual and consistent drug release. Herein, diclofenac sodium‐encapsulated PLGA nanoparticles (DS‐PLGA NPs) were synthesized, characterized, and their effects on bacterial proteolysis and elastolytic activity were evaluated using skim milk agar plate, elastin‐congo red, and staphylolysin disk susceptibility assays. Quantitative PCR was employed to examine the effect of nanoparticles on the expression of lasA/B genes. The DS‐PLGA NPs displayed spherical morphology with an average size of 86 nm, zeta potential of ‐15.2 mV, and DLS size of 124.6 nm. At a sub‐inhibitory concentration, DS‐PLGA NPs inhibited bacterial elastolytic activity by 41.6 to 62.1% during 30–180 min of incubation. The elastolytic curve slopes of samples from PLGA and DS‐PLGA treated groups were respectively 0.0714 and 0.0380 activity/min, indicating a significant reduction of bacterial extracellular elastases by DS‐PLGA NPs. Exposure of bacteria to a sub‐inhibitory concentration of the nanoparticles attenuated the expression of the lasA and lasB genes by 0.21 and 0.31 folds, respectively. Attenuation of the proteolytic activity of P. aeruginosa suggests that the antivirulence potential of the DS‐PLGA NPs along with the anti‐inflammatory properties of diclofenac sodium, can be considered for the treatment of acute and chronic P. aeruginosa infections.