Modulating release of ranibizumab and aflibercept from thiolated chitosan-based hydrogels for potential treatment of ocular neovascularization
BACKGROUND: This paper describes the synthesis of thiolated chitosan-based hydrogels with varying degrees of crosslinking that has been utilized to modulate release kinetics of two clinically relevant FDA-approved anti-VEGF protein drugs, ranibizumab and aflibercept. These hydrogels have been fabricated into disc shaped structures for potential use as patches on ocular surface.
METHODS: Protein conformational changes and aggregation after loading and release was evaluated by circular dichroism (CD), steady-state tryptophan fluorescence spectroscopy, electrophoresis and size-exclusion chromatography (SEC). Finally, the capacity of both released proteins to bind to VEGF was tested by ELISA and surface plasmon resonance (SPR) technology.
RESULTS: The study demonstrates the versatility of thiolated chitosan-based hydrogels for delivering proteins. The effect of various parameters of the hydrogel on protein release kinetics and mechanism of protein release was studied using the Korsmeyer-Peppas release model. Furthermore, we have studied the stability of released proteins in detail while comparing it with non-entrapped proteins under physiological conditions to understand the effect of formulation conditions on protein stability.
CONCLUSIONS: The disc-shaped thiolated chitosan-based hydrogels provide a potentially useful platform to deliver ranibizumab and aflibercept for the treatments of ocular diseases such as wet AMD, DME and corneal neovascularization.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Expert opinion on drug delivery - 14(2017), 8 vom: 18. Aug., Seite 913-925 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Moreno, Miguel [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.12.2017 Date Revised 02.12.2018 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/17425247.2017.1343297 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM273214489 |
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| 100 | 1 | |a Moreno, Miguel |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Modulating release of ranibizumab and aflibercept from thiolated chitosan-based hydrogels for potential treatment of ocular neovascularization |
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| 500 | |a Date Completed 12.12.2017 | ||
| 500 | |a Date Revised 02.12.2018 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: This paper describes the synthesis of thiolated chitosan-based hydrogels with varying degrees of crosslinking that has been utilized to modulate release kinetics of two clinically relevant FDA-approved anti-VEGF protein drugs, ranibizumab and aflibercept. These hydrogels have been fabricated into disc shaped structures for potential use as patches on ocular surface | ||
| 520 | |a METHODS: Protein conformational changes and aggregation after loading and release was evaluated by circular dichroism (CD), steady-state tryptophan fluorescence spectroscopy, electrophoresis and size-exclusion chromatography (SEC). Finally, the capacity of both released proteins to bind to VEGF was tested by ELISA and surface plasmon resonance (SPR) technology | ||
| 520 | |a RESULTS: The study demonstrates the versatility of thiolated chitosan-based hydrogels for delivering proteins. The effect of various parameters of the hydrogel on protein release kinetics and mechanism of protein release was studied using the Korsmeyer-Peppas release model. Furthermore, we have studied the stability of released proteins in detail while comparing it with non-entrapped proteins under physiological conditions to understand the effect of formulation conditions on protein stability | ||
| 520 | |a CONCLUSIONS: The disc-shaped thiolated chitosan-based hydrogels provide a potentially useful platform to deliver ranibizumab and aflibercept for the treatments of ocular diseases such as wet AMD, DME and corneal neovascularization | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Thiolated chitosan-based hydrogels | |
| 650 | 4 | |a aflibercept | |
| 650 | 4 | |a anti-vascular endothelial growth factor proteins | |
| 650 | 4 | |a neovascularization | |
| 650 | 4 | |a ranibizumab | |
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| 700 | 1 | |a Pow, Poh Yih |e verfasserin |4 aut | |
| 700 | 1 | |a Tabitha, Tan Su Teng |e verfasserin |4 aut | |
| 700 | 1 | |a Nirmal, Sonali |e verfasserin |4 aut | |
| 700 | 1 | |a Larsson, Andreas |e verfasserin |4 aut | |
| 700 | 1 | |a Radhakrishnan, Krishna |e verfasserin |4 aut | |
| 700 | 1 | |a Nirmal, Jayabalan |e verfasserin |4 aut | |
| 700 | 1 | |a Quah, Soo Tng |e verfasserin |4 aut | |
| 700 | 1 | |a Geifman Shochat, Susana |e verfasserin |4 aut | |
| 700 | 1 | |a Agrawal, Rupesh |e verfasserin |4 aut | |
| 700 | 1 | |a Venkatraman, Subbu |e verfasserin |4 aut | |
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