Exploring the Therapeutic Efficacy of Zingerone Nanoparticles in Treating Biofilm-Associated Pyelonephritis Caused by Pseudomonas aeruginosa in the Murine Model.

Abstract

Biofilms of Pseudomonas aeruginosa can cause complicated urinary tract infections especially in people with indwelling catheters which may result in pyelonephritis. Microorganisms in biofilm demonstrate high resistance to both antibiotics and host protection mechanisms, often resulting in chronic and difficult-to-treat infections. This study is aimed to assess in vivo and ex vivo efficacy of Zingerone nanoparticles (Z-NPs) against P. aeruginosa biofilm-associated murine acute pyelonephritis. In the present study, Zingerone and chitosan acted synergistically in the form of Z-NPs and found to be nontoxic to the kidney cell lines as depicted in MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay demonstrating their cytocompatibility. In vivo experiments indicated that Z-NPs (100mg/kg) treatment reduced P. aeruginosa pathogenicity and enhanced the clearance of bacterial count from the renal and bladder tissue. Z-NPs improved the disease outcome by lowering the levels of various inflammatory markers, and histopathological examination revealed better recovery in renal and bladder tissue. Besides, ex vivo efficacy also confirmed that Z-NPs enhanced serum bactericidal effect along with increased phagocytic uptake and intracellular killing of P. aeruginosa as confirmed by fluorescent microscopy. To the best of our knowledge, this is the first study to provide evidence that Z-NPs are effective therapeutic agents for combating P. aeruginosa associated pyelonephritis.