Controlled release of vancomycin from a thermoresponsive hydrogel system for the prophylactic treatment of postoperative acute endophthalmitis

Purpose: To investigate the efficacy of a poly(ethylene glycol) diacrylate and poly(Nisopropylacrylamide) based thermo-responsive hydrogel drug delivery system (DDS) to deliver prophylactic vancomycin (VAN) following ocular surgery. Methods: VAN was encapsulated in a hydrogel DDS and characterized in terms of initial burst, release kinetics, bioactivity, and cytotoxicity. Long-Evans rats received an intravitreal injection of Staphylococcus aureus to produce acute endophthalmitis in four experimental groups. One of four treatments were then applied: (1) bolus subconjunctival injection of VAN, (2) blank DDS, (3) saline treatment, and (4) subconjunctival injection of VAN DDS. Animals were scored for infection (0-3) at 12, 24, 48, and 72 hours, and eyes were harvested at 24 and 48 hours for histology. Results: Following a 36% initial burst, VAN release from the DDS continued at a steady rate for 2 weeks plateauing at 84% after 504 hours. Bioactivity was maintained for all release samples and cytotoxicity analysis for the DDS revealed cell viability >90%. Not until after 12 hours did any of the groups show evidence of infection; however, at 24 hours, animals that received the VAN DDS had significantly lower infection scores (0 ± 0) than those that received a bolus VAN injection, blank DDS, or saline (1.5 ± 1.5, 2.3 ± 0.87, and 2.9 ± 0.25; respectively). At 48 and 72 hours, the VAN DDS and bolus VAN treatment groups performed comparably and showed significantly better infection scores than the control groups. Conclusions: This DDS appears to have promise as a vehicle for short term, prophylactic antibiotic delivery. Translational Relevance: This DDS may prevent the development of postoperative endophthalmitis.