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Development of a novel biocompatible drug delivery platform for ophthalmic conditions

Alband, M; (2016) Development of a novel biocompatible drug delivery platform for ophthalmic conditions. Doctoral thesis , UCL.

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Glaucoma is a chronic optic neuropathy that affects an estimated 70 million people worldwide of which 7 million are blind. It is the number one cause of irreversible blindness and the only proven modifiable risk factor is raised intra-ocular pressure (IOP). Glaucoma treatment aims to reduce IOP and can be in the form of eye drops, laser or surgery. Surgery aims to increase outflow mechanism for drainage of aqueous humour from the anterior chamber. This can be in the form of glaucoma filtration surgery (GFS) or insertion of a glaucoma drainage device (GDD). GFS is complicated by scarring in the post-operative period and GDD surgery insertion is complicated by the development of a fibrous encapsulation around the device. This encapsulation initially acts as a flow control mechanism but subsequently results in device failure. Factors that may influence this include: the material surface quality, the shape of the device and the device material. 2-methacryloyloxyethyl (MPC) is used as a synthetic polymer based coating that has been demonstrated to prevent the occurrence of coronary artery stenosis. The aim of this investigation was to assess the in vitro biocompatibility of 3D printed and PC based materials compared to materials used in current ophthalmic devices. Sterility testing was performed using ethanol and autoclaving processes, commonly used techniques for the development of ophthalmic devices. Adhesion of monocytes, macrophages and fibroblasts to material surfaces was assessed using live stain, Alamar Blue and CyQUANT assays and fluorescent microscopy. Adsorption of albumin and fibrinogen was assessed using SDS Page Gel Electrophoresis, UV Photospectrometry, Fluorescein Isothiocyanate Labelled Bovine Serum Albumin (FITC-BSA) and Micro Bicinchoninic Acid (BCA) techniques. PC based materials (containing 5 and 15% MPC) were compared to Polytetrafluoroethylene (PTFE), Polyethylene Terephthalate (PET), Polymethyl Methacrylate (PMMA), Silicone, 2-hydroxyethyl methacrylate (HEMA) and a contact lens that contains 15% MPC. It was observed that PC based materials demonstrated less cellular and protein adhesion than materials used in current ophthalmic devices but more than a contact lens of similar composition. This suggests that the manufacturing process may play a role in the biocompatibility response and these studies were therefore repeated with different contact lenses based on the Food & Drug Administration (FDA) grouping of contact lenses. PC is a potential material that can be used to improve biocompatibility of ophthalmic devices. Future work will be performed to develop a novel drug delivery platform that can be used in the treatment of ophthalmic conditions.

Type: Thesis (Doctoral)
Title: Development of a novel biocompatible drug delivery platform for ophthalmic conditions
Event: UCL
Keywords: Drug Delivery, Glaucoma, 3D printing, Hydrogels, Biocompatibility
URI: https://discovery.ucl.ac.uk/id/eprint/1521389
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