The biofilm inhibition activity of a NO donor nanosilica with enhanced antibiotics action

Int J Pharm. 2021 Dec 15:610:121220. doi: 10.1016/j.ijpharm.2021.121220. Epub 2021 Oct 20.

Abstract

Nitric oxide (NO) has emerged as a promising antibacterial agent, where NO donor compounds have been explored. Here, we investigated the role of a silica nanoparticle containing nitroprusside (MPSi-NP) as a NO donor agent against methicillin-sensitive (ATCC 25,923 and ATCC 12228) and methicillin-resistant (ATCC 700,698 and ATCC 35984) Staphylococcus strains. Biofilm inhibition was studied along with antibiotic activity in combination with standard antibiotics (ampicillin and tetracycline). MPSi-NP exhibited thermal release of 63% of NO within 24 h, while free nitroprusside released only 18% during a dialysis assay, indicating an assisted release of NO mediated by the nanoparticles. This nanomaterial showed only a moderate activity in blocking biofilm production, but exhibited a significant decrease in the number of viable bacterial cells (over 600-fold for Staphylococcus aureus ATCC 700,698 and Staphylococcus epidermidis ATCC 35984). Remarkably, even using MPSi-NP at concentrations below any antibacterial action, its combination with ampicillin promoted a significant decrease in MIC for resistant strains of S. aureus ATCC 700,698 (2-fold) and S. epidermidis ATCC 35,984 (4-fold). A carbopol-based gel formulation with MPSi-NP (0.5% w/w) was prepared and showed a zone of inhibition of 7.7 ± 0.6 mm for S. epidermidis ATCC 35984. Topical use of MPSi-NP in combination with antibiotics might be a manageable strategy to prevent and eventually treat complicated resistant bacterial infections.

Keywords: Antibiotics; Biofilm; Nitroprusside; Resistance; Silica nanoparticles.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Biofilms
  • Humans
  • Methicillin-Resistant Staphylococcus aureus*
  • Microbial Sensitivity Tests
  • Nitric Oxide Donors / pharmacology
  • Renal Dialysis
  • Staphylococcal Infections*
  • Staphylococcus aureus

Substances

  • Anti-Bacterial Agents
  • Nitric Oxide Donors