Inhibition of proliferative vitreoretinopathy by a newly developed methotrexate loaded drug carrier in vitro
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222014779 |
| _version_ | 1811177254029361152 |
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| author | Sebastian S. Arrow Simone C. Felis Anna Hillenmayer Laura D. Strehle Susanna F. Koenig Efstathios Vounotrypidis Armin Wolf Christian M. Wertheimer |
| author_facet | Sebastian S. Arrow Simone C. Felis Anna Hillenmayer Laura D. Strehle Susanna F. Koenig Efstathios Vounotrypidis Armin Wolf Christian M. Wertheimer |
| author_sort | Sebastian S. Arrow |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T22:58:38Z |
| format | Article |
| id | doaj.art-026263395ee64c48b42991d15a06f44a |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-10T22:58:38Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-026263395ee64c48b42991d15a06f44a2023-01-14T04:25:41ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-02-01158114088Inhibition of proliferative vitreoretinopathy by a newly developed methotrexate loaded drug carrier in vitroSebastian S. Arrow0Simone C. Felis1Anna Hillenmayer2Laura D. Strehle3Susanna F. Koenig4Efstathios Vounotrypidis5Armin Wolf6Christian M. Wertheimer7Correspondence to: Augenklinik der Universität Ulm, Prittwitzstr. 43, 89075 Ulm, Deutschland, Germany.; Department of Ophthalmology, University Hospital Ulm, Prittwitzstraße 43, 89075 Ulm, GermanyDepartment of Ophthalmology, University Hospital Ulm, Prittwitzstraße 43, 89075 Ulm, GermanyDepartment of Ophthalmology, University Hospital Ulm, Prittwitzstraße 43, 89075 Ulm, GermanyDepartment of Ophthalmology, University Hospital Ulm, Prittwitzstraße 43, 89075 Ulm, GermanyDepartment of Ophthalmology, University Hospital Ulm, Prittwitzstraße 43, 89075 Ulm, GermanyDepartment of Ophthalmology, University Hospital Ulm, Prittwitzstraße 43, 89075 Ulm, GermanyDepartment of Ophthalmology, University Hospital Ulm, Prittwitzstraße 43, 89075 Ulm, GermanyDepartment of Ophthalmology, University Hospital Ulm, Prittwitzstraße 43, 89075 Ulm, GermanyPurpose: 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.http://www.sciencedirect.com/science/article/pii/S0753332222014779Proliferative vitreretinopathyRetinal detachmentSlow-release drug carrierMethotrexatePolylactide-co-glycolideOrphan drug |
| spellingShingle | Sebastian S. Arrow Simone C. Felis Anna Hillenmayer Laura D. Strehle Susanna F. Koenig Efstathios Vounotrypidis Armin Wolf Christian M. Wertheimer Inhibition of proliferative vitreoretinopathy by a newly developed methotrexate loaded drug carrier in vitro Biomedicine & Pharmacotherapy Proliferative vitreretinopathy Retinal detachment Slow-release drug carrier Methotrexate Polylactide-co-glycolide Orphan drug |
| title | Inhibition of proliferative vitreoretinopathy by a newly developed methotrexate loaded drug carrier in vitro |
| title_full | Inhibition of proliferative vitreoretinopathy by a newly developed methotrexate loaded drug carrier in vitro |
| title_fullStr | Inhibition of proliferative vitreoretinopathy by a newly developed methotrexate loaded drug carrier in vitro |
| title_full_unstemmed | Inhibition of proliferative vitreoretinopathy by a newly developed methotrexate loaded drug carrier in vitro |
| title_short | Inhibition of proliferative vitreoretinopathy by a newly developed methotrexate loaded drug carrier in vitro |
| title_sort | inhibition of proliferative vitreoretinopathy by a newly developed methotrexate loaded drug carrier in vitro |
| topic | Proliferative vitreretinopathy Retinal detachment Slow-release drug carrier Methotrexate Polylactide-co-glycolide Orphan drug |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222014779 |
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