Dual encapsulation of curcumin and ciprofloxacin in chitosan nanoparticles attenuates Pseudomonas aeruginosa virulence, elastinolytic potential and quorum sensing genes

Abstract

Pseudomonas aeruginosa is an important human pathogen that is responsible for various human infections and able to develop resistance to a variety of antibiotics. Drug encapsulation may provide sustained and more efficient drug delivery, particularly in case of the drugs with low bioavailability. This study aims to characterize the antivirulence and anti-quorum sensing (QS) properties of curcumin and ciprofloxacin dually encapsulated in chitosan NPs (Cur-Cip-CsNPs). The nanoparticles were synthesized and characterized by SEM, FT-IR, Zeta Potential, and DLS analyses. The antibacterial and antivirulence effects of the Cip-CsNPs, Cur-CsNPs, and Cur-Cip-CsNPs against P. aeruginosa strains were investigated by well diffusion, biofilm and pyocyanin quantification, swarming, swimming, twitching, and proteolytic and elastinolytic activity assays. The mRNA transcript levels of the lasIR and lasAB genes were also determined by real-time PCR. Cur-Cip-CsNPs were more potent antibacterial agents against P. aeruginosa compared with other NPs and inhibited bacterial planktonic growth at 160 mg/mL, reduced biofilm formation by 72.5-86.5 % and pyocyanin levels by 80.2-80.6 %, and significantly inhibited flagellar and fimbrial motility of P. aeruginosa. Furthermore, bacterial proteolysis and elastinolytic activity were reduced more efficiently by Cur-Cip-CsNPs compared with other nanoformulations. The expression of the lasI, lasR, lasA, and lasB was attenuated more efficiently by Cur-Cip-CsNPs compared with Cip-CsNPs and Cur-CsNPs. This study presents an innovative approach to overcome the challenges due to antibiotic resistance and provides a new therapeutic option against P. aeruginosa infections.

Keywords: Chitosan nanoparticles; Ciprfloxacin; Curcumin; Pseudomonas aeruginosa.