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 fabric...
| Main Authors: | , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2017
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| Online Access: | https://hdl.handle.net/10356/84063 http://hdl.handle.net/10220/42956 |
| _version_ | 1826128457256402944 |
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| author | Moreno, Miguel Pow, Poh Yih Tan, Su Teng Tabitha Nirmal, Sonali Larsson, Andreas Radhakrishnan, Krishna Nirmal, Jayabalan Quah, Soo Tng Shochat, Susana Geifman Agrawal, Rupesh Venkatraman, Subbu S. |
| author2 | School of Materials Science & Engineering |
| author_facet | School of Materials Science & Engineering Moreno, Miguel Pow, Poh Yih Tan, Su Teng Tabitha Nirmal, Sonali Larsson, Andreas Radhakrishnan, Krishna Nirmal, Jayabalan Quah, Soo Tng Shochat, Susana Geifman Agrawal, Rupesh Venkatraman, Subbu S. |
| author_sort | Moreno, Miguel |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T07:25:17Z |
| format | Journal Article |
| id | ntu-10356/84063 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:25:17Z |
| publishDate | 2017 |
| record_format | dspace |
| spelling | ntu-10356/840632020-06-01T10:13:58Z Modulating release of ranibizumab and aflibercept from thiolated chitosan-based hydrogels for potential treatment of ocular neovascularization Moreno, Miguel Pow, Poh Yih Tan, Su Teng Tabitha Nirmal, Sonali Larsson, Andreas Radhakrishnan, Krishna Nirmal, Jayabalan Quah, Soo Tng Shochat, Susana Geifman Agrawal, Rupesh Venkatraman, Subbu S. School of Materials Science & Engineering School of Biological Sciences NTU-Northwestern Institute for Nanomedicine Thiolated chitosan-based hydrogels Anti-vascular endothelial growth factor proteins 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. 2017-07-21T02:31:42Z 2019-12-06T15:37:33Z 2017-07-21T02:31:42Z 2019-12-06T15:37:33Z 2017 2017 Journal Article Moreno, M., Pow, P. Y., Tan, S. T. T., Nirmal, S., Larsson, A., Radhakrishnan, K., et al. (2017). Modulating release of ranibizumab and aflibercept from thiolated chitosan-based hydrogels for potential treatment of ocular neovascularization. Expert Opinion on Drug Delivery, 14(8), 913-925. 1742-5247 https://hdl.handle.net/10356/84063 http://hdl.handle.net/10220/42956 10.1080/17425247.2017.1343297 198048 en Expert Opinion on Drug Delivery © 2017 Informa UK Limited (trading as Taylor & Francis Group). |
| spellingShingle | Thiolated chitosan-based hydrogels Anti-vascular endothelial growth factor proteins Moreno, Miguel Pow, Poh Yih Tan, Su Teng Tabitha Nirmal, Sonali Larsson, Andreas Radhakrishnan, Krishna Nirmal, Jayabalan Quah, Soo Tng Shochat, Susana Geifman Agrawal, Rupesh Venkatraman, Subbu S. Modulating release of ranibizumab and aflibercept from thiolated chitosan-based hydrogels for potential treatment of ocular neovascularization |
| title | Modulating release of ranibizumab and aflibercept from thiolated chitosan-based hydrogels for potential treatment of ocular neovascularization |
| title_full | Modulating release of ranibizumab and aflibercept from thiolated chitosan-based hydrogels for potential treatment of ocular neovascularization |
| title_fullStr | Modulating release of ranibizumab and aflibercept from thiolated chitosan-based hydrogels for potential treatment of ocular neovascularization |
| title_full_unstemmed | Modulating release of ranibizumab and aflibercept from thiolated chitosan-based hydrogels for potential treatment of ocular neovascularization |
| title_short | Modulating release of ranibizumab and aflibercept from thiolated chitosan-based hydrogels for potential treatment of ocular neovascularization |
| title_sort | modulating release of ranibizumab and aflibercept from thiolated chitosan based hydrogels for potential treatment of ocular neovascularization |
| topic | Thiolated chitosan-based hydrogels Anti-vascular endothelial growth factor proteins |
| url | https://hdl.handle.net/10356/84063 http://hdl.handle.net/10220/42956 |
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