Inhibition of proliferative vitreoretinopathy by a newly developed methotrexate loaded drug carrier in vitro.

Repeated intravitreal injections of methotrexate for proliferative vitreoretinopathy, a rare ocular condition that can cause vision loss, have shown beneficial effects in recent clinical studies. The purpose of this study was to develop a slow-release, long-term drug carrier composed of the polymer polylactide-co-glycolide and methotrexate that can be injected intravitreally. The required composition of the drug carrier was modeled using pharmacokinetic parameters based on current literature. Release kinetics were determined using an ocular pharmacokinetic model. Epiretinal PVR-membranes were harvested during pars plana vitrectomy and subsequently transferred to cell culture. The effect of the drug carrier on cell migration was investigated using time-lapse microscopy and a scratch-induced migration assay. The colorimetric WST-1-assay and a live-dead-assay were performed to determine viability, and the BrdU-assay was applied for proliferation. The release profile showed an initial and a final burst of methotrexate with an intervening steady state that lasted 9-11 weeks. It showed inhibitory effects on pathobiological processes in human PVR-cells in vitro. Cell velocity in the time-lapse assay, migration in the scratch assay (p = 0.001), and proliferation in the BrdU assay (p = 0.027) were reduced after addition of the drug carrier. These effects occurred without causing a reduction in viability in the WST-1 assay (p > 0.99) and the live-dead assay. The methotrexate-loaded drug carrier can maintain a stable concentration for 9-11 weeks and influence the pathobiological process of PVR cells in vitro. Therefore, it represents a potential therapeutic orphan drug for PVR.

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Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Efstathios Vounotrypidis reports a relationship with Bayer Corporation that includes: speaking and lecture fees. Efstathios Vounotrypidis reports a relationship with Novartis Pharmaceuticals Corporation that includes: speaking and lecture fees. Armin Wolf reports a relationship with Allergan Irvine that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Armin Wolf reports a relationship with Boehringer Ingelheim Corp USA that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Armin Wolf reports a relationship with Bayer Corporation that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Armin Wolf reports a relationship with Alimera Sciences Inc that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Armin Wolf reports a relationship with Novartis Pharmaceuticals Corporation that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Armin Wolf reports a relationship with Oertli Instrumente AG that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Armin Wolf reports a relationship with Roche SAS that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Armin Wolf reports a relationship with Carl Zeiss AG that includes: consulting or advisory and travel reimbursement.