Experimental intracameral injection of vancomycin microparticles in rabbits

Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4125-32. doi: 10.1167/iovs.09-4694. Epub 2010 Mar 24.

Abstract

Purpose: To evaluate the in vivo toxicity and efficacy of previously developed poly-(lactide-co-glycolide)-vancomycin-based microparticles (V-MPLs) for eventual use for endophthalmitis prophylaxis during cataract surgery.

Methods: The intraocular vancomycin concentration profile was evaluated after V-MPL injection into the anterior chamber of rabbit eyes. The toxicology of V-MPLs versus MPLs alone was tested by corneal cellular counting and retinal histology. The prophylactic efficacy of the V-MPLs was evaluated by bacterial counts after introducing contaminated intraocular lenses (IOLs) together with the V-MPLs into one anterior chamber of phakic rabbit eyes or without V-MPLs in control rabbit eyes.

Results: Intraocular V-MPLs produced effective vancomycin concentrations over at least 6 hours. Corneal counts revealed no significant increase in dead cells. Retinal toxicity manifested as inflammation 3 hours after injection, reaching its maximum between 12 hours and 24 hours, decreasing by 48 hours, and completely disappearing at 72 hours. Inflammation was similar between V-MPLs and MPLs. Untreated eyes implanted with highly infected IOLs showed severe, reproducible endophthalmitis. No sign of infection was observed with infected IOLs and concomitant V-MPL treatment, supported by bacterial counts showing a significant decrease in colony-forming Staphylococcus epidermidis units in the anterior chamber and on the implant surfaces within 6 hours.

Conclusions: The present study demonstrated the release and toxicologic properties of the authors' newly developed V-MPLs in vivo. In addition, the rabbit model shows that V-MPLs are effective in reducing the risk of experimental endophthalmitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anterior Chamber / drug effects*
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / toxicity*
  • Aqueous Humor / microbiology
  • Biological Availability
  • Cell Count
  • Chromatography, High Pressure Liquid
  • Colony Count, Microbial
  • Disease Models, Animal
  • Endophthalmitis / metabolism
  • Endophthalmitis / microbiology
  • Endophthalmitis / prevention & control*
  • Endothelium, Corneal / drug effects
  • Endothelium, Corneal / pathology
  • Eye Infections, Bacterial / metabolism
  • Eye Infections, Bacterial / microbiology
  • Eye Infections, Bacterial / prevention & control*
  • Half-Life
  • Injections
  • Iris / drug effects
  • Iris / pathology
  • Lens Implantation, Intraocular
  • Lenses, Intraocular / microbiology
  • Male
  • Particle Size
  • Polyglactin 910 / administration & dosage
  • Polyglactin 910 / pharmacokinetics
  • Polyglactin 910 / toxicity*
  • Rabbits
  • Retina / drug effects
  • Retina / pathology
  • Staphylococcal Infections / metabolism
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / prevention & control*
  • Staphylococcus epidermidis / isolation & purification
  • Vancomycin / administration & dosage
  • Vancomycin / pharmacokinetics
  • Vancomycin / toxicity*

Substances

  • Anti-Bacterial Agents
  • Polyglactin 910
  • Vancomycin