Biodegradable in situ forming photocrosslinked implants for sustained protein delivery to the posterior segment of the eye

Drug delivery to the posterior segment of the eye is a significant challenge, particularly in the context of sustained drug delivery for the treatment of chronic ocular conditions. The challenge is further increased due to the fact that the anti-VEGF agents, used to treat two of the most pertinent sight-threatening conditions - age-related macular degeneration and diabetic retinopathy - are proteins. <br/><br/>This thesis shows the capacity of in situ forming implants, formed from gels that can be injected through needles suitable for intravitreal injection, to provide sustained protein release for several months, with high daily release rates. Furthermore, protein activity was maintained at a high level throughout the duration of the release studies and through modification of formulation components, injection volumes and photocrosslinking duration, it was possible to modify release profiles significantly.<br/><br/>The implants studied were also capable of degrading via hydrolysis in biodegradation studies, showed high biocompatibility when tested against a retinal cell line and the injectable gels showed the capacity to be easily sterilised through the use of a simple filtration method.<br/><br/>All of the above achievements demonstrate the potential of these in situ forming implants to be injected in a minimally invasive manner, to provide sustained release of anti-VEGF agents for several months, whilst maintaining high activity and to degrade fully, removing the need for an invasive procedure to extract them once exhausted. To that end significant work is now being carried out, with the data in this thesis an essential foundation, to continue the development of this technology.

Name dc:type.qualificationname

Doctor of Philosophy

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

Queen's University Belfast

Year dc:date.issued

2020

Author dc:creator

• Waite, David

Advisors dc:contributor.advisor

• Thakur, Raghu
• Stitt, Alan
• Jones, David

Language dc:language

eng

Identifier

oai:pure.qub.ac.uk/portal:studenttheses/88894b88-3dbc-425a-afbd-3336744c4af2

OAI identifier oai:identifier

oai:pure.qub.ac.uk/portal:studenttheses/88894b88-3dbc-425a-afbd-3336744c4af2