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A Degradable Sustained-Release Drug Delivery System for Bleb-Forming Glaucoma surgery.

Ralph J S van MechelenJarno E J WoltersSebastian FredrichChristian J F BertensMarion J J GijbelsAlbert P H J SchenningLeonard PinchukTheo G M F GorgelsHenny J M Beckers
Published in: Macromolecular bioscience (2023)
Fibrosis of the filtering bleb is one of the main causes of failure after bleb-forming glaucoma surgery. Intraoperative application of mitomycin C (MMC) is the current gold standard to reduce the fibrotic response. However, MMC is cytotoxic and one-time application is often insufficient. A sustained-release drug delivery system (DDS), loaded with MMC, might be less cytotoxic and equally or more effective. Two degradable (polycaprolactone (PCL) and polylactic-co-glycolic acid (PLGA)) MMC-loaded DDSs were developed. Release kinetics were first assessed in vitro followed by rabbit implants in conjunction with the PRESERFLO ® MicroShunt. As a control, the MicroShunt was implanted with adjunctive use of a MMC solution. Rabbits were euthanized at postoperative day (POD) 28 and 90. The PLGA and PCL DDSs released (on average) 99% and 75% of MMC, respectively. All groups showed functioning blebs until POD 90. Rabbits implanted with a DDS showed more inflammation with avascular thin-walled blebs when compared to the control. However, collagen was more loosely arranged. The PLGA DDS showed less inflammation, less foreign body response (FBR) and more complete degradation at POD 90 when compared to the PCL DDS. Further optimization with regard to dosage is required to reduce side effects to the conjunctiva. This article is protected by copyright. All rights reserved.
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