Tannin coordinated nanozyme composite-based hybrid hydrogel eye drops for prophylactic treatment of multidrug-resistant Pseudomonas aeruginosa keratitis

J Nanobiotechnology. 2022 Oct 14;20(1):445. doi: 10.1186/s12951-022-01653-w.

Abstract

Pseudomonas aeruginosa infection is a severe acute suppurative ulcer that engulfs virtually the entire tissue in a short period and leads to devastating destruction. Antibiotic therapy is a common approach for the prophylaxis and treatment of P. aeruginosa infection. However, it is often associated with serious side effects, complications, and multidrug resistance. Therefore, it has been a long-standing challenge to explore safe and effective methods for controlling P. aeruginosa infection. Herein, tannin-coordinated nanozyme composite-based hybrid hydrogels (TCNH) are developed and characterized for the prophylactic treatment of P. aeruginosa and multidrug-resistant P. aeruginosa infections using mouse keratitis as the animal model. The TCNH eye drops are constructed by photoinitiated free radical polymerization of acetylated gelatin solution containing self-synthesized tannin-coordinated Co3O4/Ag nanozyme composite. The as-prepared TCNH displays good dispersibility, peroxidase-like activity and in vitro/in vivo biocompatibility. The nanozyme composite in TCNH seems to penetrate the interior of bacteria and exhibited significant broad-spectrum antibacterial activity owing to its intrinsic and nanozymic catalytic properties. Furthermore, TCNH eye drops can be successfully applied to treat P. aeruginosa and multidrug-resistant P. aeruginosa keratitis. The findings of this study reveal the potential of tannin-coordinated nanozyme composite-based hybrid hydrogel eye drops for treating infectious diseases.

Keywords: Hydrogel eye drops; Keratitis; Multidrug-resistant; P. aeruginosa infections; Tannin-coordinated nanozymes.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Cobalt
  • Eye Infections, Bacterial* / drug therapy
  • Eye Infections, Bacterial* / microbiology
  • Eye Infections, Bacterial* / prevention & control
  • Gelatin / pharmacology
  • Hydrogels
  • Keratitis* / drug therapy
  • Keratitis* / microbiology
  • Keratitis* / prevention & control
  • Mice
  • Ophthalmic Solutions / pharmacology
  • Ophthalmic Solutions / therapeutic use
  • Oxides
  • Peroxidases
  • Pseudomonas Infections* / drug therapy
  • Pseudomonas Infections* / prevention & control
  • Pseudomonas aeruginosa
  • Tannins / pharmacology
  • Tannins / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Hydrogels
  • Ophthalmic Solutions
  • Oxides
  • Tannins
  • cobalt tetraoxide
  • Cobalt
  • Gelatin
  • Peroxidases