# The effectiveness of hydrogel matrix containing nitric oxide, silver nanoparticles, vancomycin, and ciprofloxacin on methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa biofilm isolated from patients with chronic rhinosinusitis

## TL;DR

A new hydrogel containing multiple antibiotics and silver nanoparticles effectively reduces biofilms from bacteria causing chronic sinusitis, with low toxicity to human cells.

## Contribution

A thermosensitive hydrogel (HyNSVC) was developed for sustained co-release of multiple antibiofilm agents against drug-resistant bacteria in chronic rhinosinusitis.

## Key findings

- HyNSVC reduced mature biofilm by 62% in Pseudomonas aeruginosa and 68.1% in MRSA at 2× MIC.
- HyNSVC showed no significant toxicity to human A549 epithelial cells at MIC concentration.
- The hydrogel exhibited a porous structure with interconnected pores and a porosity of 80–90%.

## Abstract

Many scientists are studying chronic rhinosinusitis (CRS) due to its high relapse incidence and drug resistance. We investigated the antibiofilm activity and sustained co-release of nitric oxide, silver nanoparticles, vancomycin, and ciprofloxacin in thermosensitive hydrogel (HyNSVC) for bacterial CRS.

To identify and isolate Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA), samples were taken from 10 patients with CRS who underwent Functional Endoscopic Sinus Surgery (FESS), and then they were diagnosed using culture and molecular methods. The HyNSVC was synthesized, and its physicochemical characteristics were evaluated using different methods. The broth microdilution assay and the MTP (microtiter plate) method assessed the minimum inhibitory concentration (MIC) and antibiofilm effects. The inhibitory impact of HyNSVC on the expression of biofilm-associated genes was evaluated using real-time PCR. The cytotoxic effect of HyNSVC on the human epithelial cell line A549 was assessed.

The results of the SEM showed that the hydrogels have a porous structure and that the pores are interconnected. The molecular weights and polydispersity index (PDI) of the copolymer determined using gel permeation chromatography (GPC) were 5759 Daltons, 6270 Daltons, and 1.089, respectively. The anticipated molecular weight determined by H-NMR spectroscopy was around 5947 Daltons. Also, the porosity of the hydrogels was in the range of 80–90%. The HyNSVC MIC was 250 µg/ml for both bacteria. The 2 × MIC of HyNSVC reduced mature biofilm by 62% in P. aeruginosa and 68.1% in MRSA. The presence of HyNSVC did not significantly reduce gene expression. Finally, the MTT experiment showed no toxicity against A549 cells at the MIC concentration.

Our findings illustrated the efficacy of employing HyNSVC for drug release regulation and antibiofilm activity for bacterial infection, suggesting a promising treatment for CRS.

The online version contains supplementary material available at 10.1186/s40001-025-03282-z.