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Emily Dosmar, William F Mieler, Jennifer J Kang-Mieler; Controlled release of vancomycin from a thermoresponsive hydrogel system for the prophylactic treatment of post-operative acute endopthalmitis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5505.
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The purpose of this study was to investigate the efficacy of a poly(ethylene glycol) diacrylate (PEG-DA) and poly(N-isopropylacrylamide) (NIPAAm) based thermoresponsive hydrogel drug delivery system (DDS) to deliver prophylactic vancomycin (VAN) for two weeks following ocular surgery.
Long-Evans rats (200-250g) received an intravitreal injection of Staphylococcus aureus bacteria (5 µL, ~85 CFU) to produce an acute endopthalmitis model. VAN (60 mg) was encapsulated into thermoresponsive PEG-DA and NIPAAM based hydrogel DDSs. There were four experimental groups: 1) bolus subconjunctival injection of VAN (0.08 mg/5 µL), 2) a blank DDS (5 µL), 3) saline treatment (5 µL), and 4) subconjunctival injection of the VAN DDS (0.175 mg/5 µL). VAN treatment was administered on the same day as infection induction. Animals were assessed at 12, 24, 48, and 72 hours for signs of infection progression. Eyes at 24 and 48 hours post-treatment were harvested for histology. The level of infection was evaluated by clinical scoring methods based on slit lamp examination. The cornea, conjunctiva, and vitreous were all given scores from 0-3 where 0 indicated no signs of infection and 3 indicated edemas in the conjunctiva, an opaque cornea, and no red reflex in the vitreous.
At 12 hours after bacteria injection, none of the groups showed signs of a completely developed infection (infection scores of 0). However, at 24 hours, animals that received the VAN DDS had significantly lower (P<0.01) 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 for VAN injection, blank DDS, and bolus saline injection; respectively). At 48 and 72 hours, the VAN DDS and bolus VAN injection treatment groups performed comparably and showed significantly better (P<0.05) infection scores than the two control groups (blank DDS or saline treatment).
This study demonstrated that a thermoresponsive PEG-DA and NIPAAm based hydrogel DDS loaded with VAN may have promise for application as a vehicle for short term, prophylactic antibiotic ocular drug delivery.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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