Peptide Nanofiber System for Sustained Delivery of Anti-VEGF Proteins to the Eye Vitreous
Ranibizumab is a recombinant VEGF-A antibody used to treat the wet form of age-related macular degeneration. It is intravitreally administered to ocular compartments, and the treatment requires frequent injections, which may cause complications and patient discomfort. To reduce the number of injecti...
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MDPI AG
2023-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/4/1264 |
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| author | Seher Yaylaci Erdem Dinç Bahri Aydın Ayse B. Tekinay Mustafa O. Guler |
| author_facet | Seher Yaylaci Erdem Dinç Bahri Aydın Ayse B. Tekinay Mustafa O. Guler |
| author_sort | Seher Yaylaci |
| collection | DOAJ |
| description | Ranibizumab is a recombinant VEGF-A antibody used to treat the wet form of age-related macular degeneration. It is intravitreally administered to ocular compartments, and the treatment requires frequent injections, which may cause complications and patient discomfort. To reduce the number of injections, alternative treatment strategies based on relatively non-invasive ranibizumab delivery are desired for more effective and sustained release in the eye vitreous than the current clinical practice. Here, we present self-assembled hydrogels composed of peptide amphiphile molecules for the sustained release of ranibizumab, enabling local high-dose treatment. Peptide amphiphile molecules self-assemble into biodegradable supramolecular filaments in the presence of electrolytes without the need for a curing agent and enable ease of use due to their injectable nature—a feature provided by shear thinning properties. In this study, the release profile of ranibizumab was evaluated by using different peptide-based hydrogels at varying concentrations for improved treatment of the wet form of age-related macular degeneration. We observed that the slow release of ranibizumab from the hydrogel system follows extended- and sustainable release patterns without any dose dumping. Moreover, the released drug was biologically functional and effective in blocking the angiogenesis of human endothelial cells in a dose-dependent manner. In addition, an in vivo study shows that the drug released from the hydrogel nanofiber system can stay in the rabbit eye’s posterior chamber for longer than a control group that received only a drug injection. The tunable physiochemical characteristics, injectable nature, and biodegradable and biocompatible features of the peptide-based hydrogel nanofiber show that this delivery system has promising potential for intravitreal anti-VEGF drug delivery in clinics to treat the wet form age-related macular degeneration. |
| first_indexed | 2024-03-11T04:38:07Z |
| format | Article |
| id | doaj.art-4498d21fc9944f1c99c20301003c02e7 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T04:38:07Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-4498d21fc9944f1c99c20301003c02e72023-11-17T20:55:02ZengMDPI AGPharmaceutics1999-49232023-04-01154126410.3390/pharmaceutics15041264Peptide Nanofiber System for Sustained Delivery of Anti-VEGF Proteins to the Eye VitreousSeher Yaylaci0Erdem Dinç1Bahri Aydın2Ayse B. Tekinay3Mustafa O. Guler4Faculty of Medicine, Lokman Hekim University, Ankara 06800, TurkeyDepartment of Ophthalmology, Faculty of Medicine, Mersin University, Mersin 33000, TurkeyDepartment of Ophthalmology, Faculty of Medicine, Gazi University, Ankara 06560, TurkeyRequalite GmbH, Jahnplatz 4, 82166 Gräfelfing, GermanyPritzker School of Molecular Engineering, University of Chicago, 5640 S. Ellis Avenue, Chicago, IL 60637, USARanibizumab is a recombinant VEGF-A antibody used to treat the wet form of age-related macular degeneration. It is intravitreally administered to ocular compartments, and the treatment requires frequent injections, which may cause complications and patient discomfort. To reduce the number of injections, alternative treatment strategies based on relatively non-invasive ranibizumab delivery are desired for more effective and sustained release in the eye vitreous than the current clinical practice. Here, we present self-assembled hydrogels composed of peptide amphiphile molecules for the sustained release of ranibizumab, enabling local high-dose treatment. Peptide amphiphile molecules self-assemble into biodegradable supramolecular filaments in the presence of electrolytes without the need for a curing agent and enable ease of use due to their injectable nature—a feature provided by shear thinning properties. In this study, the release profile of ranibizumab was evaluated by using different peptide-based hydrogels at varying concentrations for improved treatment of the wet form of age-related macular degeneration. We observed that the slow release of ranibizumab from the hydrogel system follows extended- and sustainable release patterns without any dose dumping. Moreover, the released drug was biologically functional and effective in blocking the angiogenesis of human endothelial cells in a dose-dependent manner. In addition, an in vivo study shows that the drug released from the hydrogel nanofiber system can stay in the rabbit eye’s posterior chamber for longer than a control group that received only a drug injection. The tunable physiochemical characteristics, injectable nature, and biodegradable and biocompatible features of the peptide-based hydrogel nanofiber show that this delivery system has promising potential for intravitreal anti-VEGF drug delivery in clinics to treat the wet form age-related macular degeneration.https://www.mdpi.com/1999-4923/15/4/1264ranibizumabsustained drug releasehydrogelspeptide nanofiberage-related macular degeneration |
| spellingShingle | Seher Yaylaci Erdem Dinç Bahri Aydın Ayse B. Tekinay Mustafa O. Guler Peptide Nanofiber System for Sustained Delivery of Anti-VEGF Proteins to the Eye Vitreous Pharmaceutics ranibizumab sustained drug release hydrogels peptide nanofiber age-related macular degeneration |
| title | Peptide Nanofiber System for Sustained Delivery of Anti-VEGF Proteins to the Eye Vitreous |
| title_full | Peptide Nanofiber System for Sustained Delivery of Anti-VEGF Proteins to the Eye Vitreous |
| title_fullStr | Peptide Nanofiber System for Sustained Delivery of Anti-VEGF Proteins to the Eye Vitreous |
| title_full_unstemmed | Peptide Nanofiber System for Sustained Delivery of Anti-VEGF Proteins to the Eye Vitreous |
| title_short | Peptide Nanofiber System for Sustained Delivery of Anti-VEGF Proteins to the Eye Vitreous |
| title_sort | peptide nanofiber system for sustained delivery of anti vegf proteins to the eye vitreous |
| topic | ranibizumab sustained drug release hydrogels peptide nanofiber age-related macular degeneration |
| url | https://www.mdpi.com/1999-4923/15/4/1264 |
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