Abstract
Purpose :
Corneal injury, arising from surgery or trauma, cause tremendous pain. A soft bandage contact lens provides mechanical protection from the blinking lids while allowing the patient to continue to use their normal vision. It would be immensely beneficial if these bandage lenses could also deliver ophthalmic drugs to aid wound closure. Multiple studies have shown elevated levels of matrix metalloproteinase (MMP) enzymes, particularly MMP-9 and MMP-2, in a corneal wound. The purpose of this study was to evaluate the release of a corneal wound healing agent, Bovine Lactoferrin (BLF), from a MMP-9 triggered drug delivery material at a normal corneal temperature that could aid corneal injury.
Methods :
Gelatin methacrylate (GelMA) and photoinitiator (Irgacure 2959) were mixed together in PBS to obtain a solution with 30% (w/v) of GelMA. The mixture was incubated at 60°C for 48 hours. BLF was added to the mixture and centrifuged for 10 mins at 5000 rpm. The mixture was incubated for another 30 mins at 60°C before being pipetted into a mould, and then incubated at 4°C for 1 h, and then polymerized in a UV chamber for 5 mins (GelMA+) producing circular shaped discs (diameter = 6 mm, thickness = 650 µm). The samples (n=4) were washed in 1 mL of PBS for 24 hours to remove any loosely bound drug. After washing, the samples were placed in varying concentrations of MMP-9 at 37°C for 5 days. At t = 0, 1, 12, 24, 48, 72, 96, 120 hours, 200 μL of the release media was withdrawn and the amount of BLF determined by ELISA.
Results :
The BLF released increased over time (p<0.0001) and with increasing concentrations of MMP-9 (p<0.0001). This indicates that MMP-9 degraded the 30% (w/v) GelMA+ material to facilitate the release of the bound wound healing agent from the polymer network. Overall, the drug release was sustained for the entire 5 day period for all MMP-9 concentrations (p<0.001).
Conclusions :
GelMA+ is a biocompatible material that is suitable for delivering therapeutics. The results suggest that increased concentrations of MMP-9 lead to an increase in BLF release. Results support that GelMA+ could be used as an enzyme-triggered ocular drug delivery.
This is a 2021 ARVO Annual Meeting abstract.