Injectable hydrogels as matrix to retain microparticles for controlled delivery of anti-VEGF proteins for ocular applications

• Main Author: Chong, Wei Woon
• Other Authors: Subramanian Venkatraman
• Format: Final Year Project
• Language: English
• Published: 2017
• Subjects: DRNTU::Engineering::Materials
• Online Access: http://hdl.handle.net/10356/70120
• Institution: Nanyang Technological University

Wet age-related macular degeneration (AMD) or diabetic macular edema (DME) are potentially retinal diseases and they are treated by monthly or bimonthly intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents such as aflibercept (Eylea®) and ranibizumab (Lucentis®). Because of the complications associated with repeated intra-vitreal injections, there is considerable interest in developing a sustained delivery system. This work describes the preparation of injectable hydrogels with anti-VEGF protein loaded polymeric microparticles to control the release for an extended period of time to increase patients’ compliance. Chitosan-oxidized alginate was developed to serve as a matrix to carry Eylea® loaded chitosan microparticles, preventing an initial large burst of drugs and achieving a controlled drug release. Firstly, chitosan-oxidized alginate hydrogel was produced by chemically crosslinking glycol chitosan with oxidized alginate of varying degree of oxidation. Gelation time and swelling ratio were carried out to determine the degree of crosslinked structure formed from different oxidized alginate. Secondly, chitosan was ionically crosslinked with Tripolyphosphate (TPP) and covalently crosslinked with glutaraldehyde to form microparticles . Chitosan microparticles were fabricated by SPG membrane technology and various factors like type of solvent, stabilizer, pH of TPP and washing methods were studied to optimize the production of well-defined microparticles. The fabricated hydrogels and microparticles were analysed via Scanning Electron Microscopy (SEM) and Fourier Transform Infra-red Spectroscop (FTIR) to observe the morphology and observe the crosslink bonds that were formed during the process. In vitro Eylea® release experiments were conducted to study protein release profile over at least 2 weeks.