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oai:figshare.com:article/32805887 2026-10-01T16:12:09Z portal_1172 item_type_8 month_year_10_2026

Formulation and characterisation of in situ forming ocular depot implants for sustained protein delivery Ge Jiang (2792095) PUREID: 690127083 Intravitreal drug delivery sustained drug release crosslink polymer network protein stability protein characterisation Neovascular ocular diseases, including age-related macular degeneration (AMD), diabetic retinopathy (DR), diabetic macular oedema (DME) and retinal vein occlusion (RVO), are major causes of visual impairment and blindness worldwide. Ranibizumab is a widely used anti-vascular endothelial growth factor (anti-VEGF) therapy for these conditions; however, its short intravitreal half-life necessitates monthly injections, which increase treatment burden, reduce patient compliance, and raise the risk of injection-related complications. Therefore, there is a need for long-acting ocular drug delivery systems capable of providing sustained protein release while maintaining protein stability.This thesis investigated the development and characterisation of photocrosslinkable in situ forming ocular depot implants (ISFODIs) for long-term intravitreal delivery of ovalbumin (OVA), a model protein for ranibizumab. The ISFODIs consisted of PEGDA 700, PLGA, organic solvents, OVA and the photoinitiator Irgacure 819, combining solvent-induced phase inversion and photocrosslinking to form injectable depots following administration through a 27-gauge needle.Formulation optimisation demonstrated that phase inversion behaviour and photocrosslink density were critical determinants of depot performance. ISFODIs containing 10% w/w triacetin and 39.9% w/w PEGDA 700 exhibited slower phase inversion, greater matrix compactness, reduced burst release and sustained OVA release for up to 4.5 months. Increasing the concentration of Irgacure 819 from 0.1% to 0.5% w/w further enhanced crosslink density and prolonged OVA release to six months. Magnesium carbonate (MgCO3) was incorporated as an acid-neutralising additive to mitigate acidic degradation products generated by PLGA hydrolysis. While its effect on overall release behaviour was limited, MgCO₃ showed modest evidence of delaying protein degradation and aggregation during prolonged incubation.<br><br>Overall, this work demonstrates the potential of ISFODIs as a minimally invasive, long-acting protein delivery platform for posterior ocular diseases and provides important insights into the formulation factors governing sustained release and protein stability.<br><br><i>Thesis embargoed until 31st July 2031</i> 2026-10-01T16:12:09Z Text Thesis 10.17034/32805887.v1 https://figshare.com/articles/thesis/Formulation_and_characterisation_of_in_situ_forming_ocular_depot_implants_for_sustained_protein_delivery/32805887 All Rights Reserved Open Access after 2031-07-31