期刊
EXPERT OPINION ON DRUG DELIVERY
卷 14, 期 8, 页码 913-925出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/17425247.2017.1343297
关键词
Thiolated chitosan-based hydrogels; anti-vascular endothelial growth factor proteins; ranibizumab; aflibercept; neovascularization; release studies
资金
- National Thematic Research Grant
- Ageing Research Grant
- NTU-NU Institute for Nanotechnology (NNIN), Northwestern University, USA
- Nanyang Technological University, Singapore
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
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