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Title: Modulating release of ranibizumab and aflibercept from thiolated chitosan-based hydrogels for potential treatment of ocular neovascularization
Authors: 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.
Keywords: Thiolated chitosan-based hydrogels
Anti-vascular endothelial growth factor proteins
Issue Date: 2017
Source: 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.
Series/Report no.: Expert Opinion on Drug Delivery
Abstract: 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.
ISSN: 1742-5247
DOI: 10.1080/17425247.2017.1343297
Rights: © 2017 Informa UK Limited (trading as Taylor & Francis Group).
Fulltext Permission: none
Fulltext Availability: No Fulltext
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