Biocompatible hyaluronic acid-divinyl sulfone injectable hydrogels for sustained drug release with enhanced antibacterial properties against Staphylococcus aureus

Mater Sci Eng C Mater Biol Appl. 2021 Jun:125:112102. doi: 10.1016/j.msec.2021.112102. Epub 2021 Apr 16.

Abstract

Hyaluronic acid (HA) solutions were crosslinked with divinyl sulfone (DVS) and subsequently loaded with antibiotic molecules to obtain biocompatible and antibacterial injectable hydrogels. The crosslinking degree of the hydrogels was modulated by varying the reaction time and the HA:DVS weight ratio. Synthesized HA-DVS hydrogels were characterized by their rheological properties, pore size, swelling capacity and hydrolytic and thermal degradation. Biocompatibility was assessed by measuring pH, osmolality and by in vitro cytotoxic assay. Acetyl salicylic (AAS) loaded hydrogels display anti-inflammatory properties in vitro, whereas cefuroxime (CFX), tetracycline (TCN) and amoxicillin (AMX) loaded hydrogels show in vitro antibacterial activity against Staphylococcus aureus. The combine use of antibiotics and AAS produces a synergic effect that reduces the S. aureus population up to a log10 reduction (R) of 5.55. Overall results show that antibiotic/AAS loaded HA-DVS hydrogels could be effectively used to combat S. aureus infections and to increase the antibacterial activity of antibiotics commonly used against S. aureus.

Keywords: Acetylsalicylic acid; Antibiotics; Drug delivery; Hyaluronic acid; Injectable hydrogels; Staphylococcus aureus.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Drug Liberation
  • Hyaluronic Acid*
  • Hydrogels*
  • Materials Testing
  • Staphylococcus aureus
  • Sulfones

Substances

  • Anti-Bacterial Agents
  • Hydrogels
  • Sulfones
  • divinyl sulfone
  • Hyaluronic Acid