TY - DATA T1 - Modulating release of ranibizumab and aflibercept from thiolated chitosan-based hydrogels for potential treatment of ocular neovascularization PY - 2017/08/11 AU - Miguel Moreno AU - Poh Yih Pow AU - Tan Su Teng Tabitha AU - Sonali Nirmal AU - Andreas Larsson AU - Krishna Radhakrishnan AU - Jayabalan Nirmal AU - Soo Tng Quah AU - Susana Geifman Shochat AU - Rupesh Agrawal AU - Subbu Venkatraman UR - https://tandf.figshare.com/articles/journal_contribution/Modulating_release_of_ranibizumab_and_aflibercept_from_thiolated_chitosan-based_hydrogels_for_potential_treatment_of_ocular_neovascularization/5302954 DO - 10.6084/m9.figshare.5302954.v1 L4 - https://tandf.figshare.com/ndownloader/files/9080839 KW - Thiolated chitosan-based hydrogels KW - anti-vascular endothelial growth factor proteins KW - ranibizumab KW - aflibercept KW - neovascularization KW - release studies N2 - 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 ER -