Experimental intracameral injection of vancomycin microparticles in rabbits

• Published in: Investigative ophthalmology & visual science 2010-08, Vol.51 (8), p.4125-4132
• Main Authors: Kodjikian, Laurent, Couprie, Jérémy, Hachicha, Walid, Timour, Quadiri, Devouassoux, Mojgan, Builles, Nicolas, Hartmann, Daniel, Fessi, Hatem
• Format: Article
• Language: English
• Subjects: 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; Chemical and Process Engineering; Chromatography, High Pressure Liquid; Colony Count, Microbial; Disease Models, Animal; Endophthalmitis - metabolism; Endophthalmitis - microbiology; Endophthalmitis - prevention & control; Endothelium, Corneal - drug effects; Endothelium, Corneal - pathology; Engineering Sciences; 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; Life Sciences; Male; Particle Size; Pharmaceutical sciences; 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
• ISSN: 1552-5783; 0146-0404; 1552-5783
• DOI: 10.1167/iovs.09-4694

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. 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. 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. 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.