Inhibition of proliferative vitreoretinopathy by a newly developed methotrexate loaded drug carrier in vitro - 13/01/23
, Simone C. Felis 1, Anna Hillenmayer, Laura D. Strehle, Susanna F. Koenig, Efstathios Vounotrypidis, Armin Wolf, Christian M. WertheimerAbstract |
Purpose |
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.
Methods |
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.
Results |
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.
Conclusion |
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.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | A drug carrier with methotrexate for proliferative vitreoretinopathy was designed |
• | The drug carrier maintained a stable concentration in a pharmacokinetic eye model |
• | The drug carrier exhibited similar release kinetics in salt solution and silicon oil |
• | Inhibitory effects on proliferative vitreoretinopathy were demonstrated in vitro |
• | The drug carrier has the potential to inhibit proliferative vitreoretinopathy |
Keywords : Proliferative vitreretinopathy, Retinal detachment, Slow-release drug carrier, Methotrexate, Polylactide-co-glycolide, Orphan drug
Plan
Vol 158
Article 114088- février 2023 Retour au numéro
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