Antibiotic-free ocular sterilization while suppressing immune response to protect corneal transparency in infectious keratitis treatment

J Control Release. 2024 Oct:374:563-576. doi: 10.1016/j.jconrel.2024.08.038. Epub 2024 Aug 30.

Abstract

Clinical guidelines for infectious keratitis treatment require that anti-inflammatory drugs can only be used after infection elimination, which causes irreversible inflammatory damage to the cornea. In this work, photodynamic metal organic frameworks (PCN-224) were used as drug carrier to load Pt NPs with catalase-like activity and anti-inflammatory drug (Dexamethasone, DXMS) for endogenous oxygen generation and reduced corneal damage, respectively. The photodynamic therapy (PDT) effect was greatly enhanced in bacteria elimination and bacterial biofilms removal through catalysis of overexpressed hydrogen peroxide (H2O2, ∼8.0 and 31.0 μM in bacterial solution and biofilms, respectively) into oxygen by Pt NPs. More importantly, the cationic liposome modified PCN-224@Pt@DXMS@Liposomes (PPDL NPs) greatly enhanced the adhesion to negatively charged ocular surface and penetration into corneal barrier and bacterial biofilms. Both in vitro cell viability test and in vivo eye irritation tests proved good biocompatibility of PPDL NPs under 660 nm laser irradiation. Furthermore, PDT of PPDL NPs in rapid bacteria killing was verified through infectious keratitis animal model. The superior bactericidal effect of antibacterial materials could largely replace the bactericidal effect of the immune system. It is worth mentioning that this simultaneous sterilization and anti-inflammation treatment mode is a new exploration against the clinical treatment guidelines.

Keywords: Biofilms; Cationic liposome; Corneal barrier; Infectious keratitis; Photodynamic therapy.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacology
  • Anti-Inflammatory Agents* / administration & dosage
  • Anti-Inflammatory Agents* / pharmacology
  • Biofilms* / drug effects
  • Cell Survival / drug effects
  • Cornea* / drug effects
  • Cornea* / microbiology
  • Dexamethasone* / administration & dosage
  • Dexamethasone* / therapeutic use
  • Drug Carriers / chemistry
  • Female
  • Humans
  • Hydrogen Peroxide
  • Keratitis* / drug therapy
  • Keratitis* / immunology
  • Keratitis* / microbiology
  • Liposomes*
  • Metal Nanoparticles / administration & dosage
  • Metal Nanoparticles / chemistry
  • Metal-Organic Frameworks / administration & dosage
  • Metal-Organic Frameworks / chemistry
  • Mice
  • Photochemotherapy* / methods
  • Photosensitizing Agents / administration & dosage
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / therapeutic use
  • Rabbits
  • Sterilization / methods

Substances

  • Dexamethasone
  • Liposomes
  • Anti-Inflammatory Agents
  • Metal-Organic Frameworks
  • Anti-Bacterial Agents
  • Hydrogen Peroxide
  • Photosensitizing Agents
  • Drug Carriers