ISMN-loaded PLGA-PEG nanoparticles conjugated with anti- Staphylococcus aureus α-toxin inhibit Staphylococcus aureus biofilms in chronic rhinosinusitis

Future Med Chem. 2021 Dec;13(23):2033-2046. doi: 10.4155/fmc-2021-0126. Epub 2021 Oct 6.

Abstract

Background:Staphylococcus aureus biofilms were linked to negative postsurgical outcomes of chronic rhinosinusitis (CRS). This study aims to develop a targeted nanoparticle and characterize its bactericidal effects. Methods: The authors prepared ISMN-loaded poly-lactide-co-glycolide acid (PLGA) and polyethylene glycol (PEG) nanoparticles conjugated with anti-S. aureus α-toxin (AA; ISMN-PLGA-PEG-AA), and determined its bactericidal and toxic effects. The antibiofilm propriety of ISMN-PLGA-PEG-AA was further investigated in a sheep CRS model. Results: ISMN-PLGA-PEG-AA had no toxic effect, while ISMN, ISMN-PLGA-PEG and ISMN-PLGA-PEG-AA had significantly anti-S. aureus effects. The blood concentrations and mRNA levels in sinus tissues of IL-4, IL-8 and IFN-γ in the sheep CRS model were significantly low. Conclusion: ISMN-PLGA-PEG-AA can effectively inhibit S. aureus biofilm, and is a promising drug for CRS treatment.

Keywords: PLGA-PEG; Staphylococcus aureus; chronic rhinosinusitis; isosorbide mononitrate; sheep.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Biofilms / drug effects
  • Chronic Disease
  • Isosorbide Dinitrate / analogs & derivatives*
  • Isosorbide Dinitrate / chemistry
  • Isosorbide Dinitrate / pharmacology
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Nanoparticles / chemistry*
  • Polyesters / chemistry
  • Polyesters / pharmacology*
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacology*
  • Rhinitis / drug therapy*
  • Rhinitis / microbiology
  • Staphylococcus aureus / drug effects*

Substances

  • Anti-Bacterial Agents
  • Polyesters
  • polyethylene glycol-poly(lactide-co-glycolide)
  • Polyethylene Glycols
  • Isosorbide Dinitrate
  • isosorbide-5-mononitrate