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A Degradable Sustained-Release Drug Delivery System for Bleb-Forming Glaucoma Surgery |
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| Authors: | Ralph JS van Mechelen Jarno EJ Wolters Sebastian Fredrich Christian JF Bertens Marion JJ Gijbels Albert PHJ Schenning Leonard Pinchuk Theo GMF Gorgels Henny JM Beckers |
| Institution: | 1. University Eye Clinic Maastricht, Maastricht University Medical Center+ (MUMC+), Maastricht, 6202 AZ The Netherlands;2. University Eye Clinic Maastricht, Maastricht University Medical Center+ (MUMC+), Maastricht, 6202 AZ The Netherlands
School for Mental Health and Neuroscience, Maastricht University, Maastricht, 6229 ER The Netherlands;3. Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Amsterdam Infection and Immunity, Amsterdam UMC, A.M. Vree G1-146, Amsterdam, 1100 DD Netherlands;4. School for Mental Health and Neuroscience, Maastricht University, Maastricht, 6229 ER The Netherlands Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Amsterdam Infection and Immunity, Amsterdam UMC, A.M. Vree G1-146, Amsterdam, 1100 DD Netherlands;5. Laboratory of Stimuli-responsive Functional Materials and Devices, Department of Chemical Engineering and Chemistry, Technical University of Eindhoven, Eindhoven, 5600 MB The Netherlands;6. InnFocus Inc. a Santen company, 12415 S.W. 136 Avenue, Miami, FL, 33186 USA |
| Abstract: | 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, may be less cytotoxic and equally or more effective. Two degradable (polycaprolactone (PCL) and polylactic-co-glycolic acid (PLGA)) MMC-loaded DDSs are developed. Release kinetics are first assessed in vitro followed by rabbit implants in conjunction with the PRESERFLO MicroShunt. As a control, the MicroShunt is implanted with adjunctive use of a MMC solution. Rabbits are euthanized at postoperative day (POD) 28 and 90. The PLGA and PCL DDSs release (on average) 99% and 75% of MMC, respectively. All groups show functioning blebs until POD 90. Rabbits implanted with a DDS show more inflammation with avascular thin-walled blebs when compared to the control. However, collagen is more loosely arranged. The PLGA DDS shows 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. |
| Keywords: | drug delivery system fibrosis glaucoma glaucoma filtration surgery mitomycin C |