Modulating release of ranibizumab and aflibercept from thiolated chitosan-based hydrogels for potential treatment of ocular neovascularization

• Main 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.
• Other Authors: School of Materials Science & Engineering
• Format: Article
• Language: English
• Published: 2017
• Subjects: Thiolated chitosan-based hydrogels; Anti-vascular endothelial growth factor proteins
• Online Access: https://hdl.handle.net/10356/84063; http://hdl.handle.net/10220/42956
• Institution: Nanyang Technological University

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.