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A Degradable Sustained-Release Drug Delivery System for Bleb-Forming Glaucoma Surgery
Ralph J S van Mechelen1,2, Jarno E J Wolters1,2, Sebastian Fredrich3
1University Eye Clinic Maastricht, Maastricht University Medical Center+ (MUMC+), Maastricht, 6202 AZ, The Netherlands.
Macromolecular Bioscience
|May 30, 2023
Summary
New drug delivery systems using mitomycin C (MMC) show promise for glaucoma surgery. These systems may reduce bleb fibrosis, a common cause of surgical failure, potentially offering a less toxic alternative to current treatments.
Area of Science:
- Ophthalmology
- Biomaterials Science
- Drug Delivery Systems
Background:
- Fibrosis of filtering blebs is a primary cause of failure in glaucoma surgery.
- Current standard treatment involves intraoperative mitomycin C (MMC), which is cytotoxic and often requires multiple applications.
- There is a need for safer and more effective methods to control the fibrotic response.
Purpose of the Study:
- To develop and evaluate biodegradable, sustained-release drug delivery systems (DDS) for MMC.
- To compare the efficacy and safety of MMC-loaded polycaprolactone (PCL) and polylactic-co-glycolic acid (PLGA) DDSs against conventional MMC solution in a rabbit glaucoma surgery model.
- To assess the impact of these DDSs on bleb function, inflammation, and tissue response.
Main Methods:
- Two types of biodegradable DDSs (PCL and PLGA) were loaded with MMC.
- In vitro release kinetics were assessed.
- Rabbit models received the PRESERFLO MicroShunt with either PCL-MMC DDS, PLGA-MMC DDS, or conventional MMC solution.
- Bleb morphology, function, inflammation, and foreign body response were evaluated at postoperative days 28 and 90.
Main Results:
- PLGA DDS released 99% of MMC, while PCL DDS released 75%.
- All surgical groups maintained functioning blebs through postoperative day 90.
- DDS groups exhibited more inflammation and avascular blebs but with looser collagen arrangement compared to controls.
- The PLGA DDS demonstrated less inflammation and foreign body response, with more complete degradation by day 90.
Conclusions:
- Sustained-release MMC DDSs are feasible for glaucoma surgery, potentially reducing bleb fibrosis.
- The PLGA DDS showed a favorable profile regarding inflammation and degradation compared to the PCL DDS.
- Further dose optimization is necessary to mitigate conjunctival side effects.
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