Hyaluronic acid based light responsive long acting hydrogel for the intraocular delivery of spironolactone

Chorio-retinal diseases, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR), are responsible for irreversible vision loss worldwide. Non-VEGF pathways, such as the renin-angiotensin-aldosterone system (RAAS), show promise as therapeutic targets for retinal diseases to address the increasing non-responder population to anti-VEGF therapy for DR. Elevated renin levels in DR are linked to retinal angiogenesis and inflammation. Spironolactone (SPL) has demonstrated the potential to reduce angiogenesis. A sustained delivery approach could be beneficial for chronic ocular disorders by delivering the therapeutic dose over a longer duration, thus reducing the frequency of intravitreal administration. Hence, a light responsive methacrylated hyaluronic acid (MEHA) polymer was synthesised and used to develop an in situ gelling depot that provides sustained release of SPL upon UV crosslinking. The in vitro release of SPL from the light responsive in situ depot was seen over 90 days. Furthermore, the in vivo ocular residence studies have demonstrated the depot remaining for >60 days. The SPL-loaded light responsive hydrogel demonstrated in vivo safety and efficacy against DR, further supporting its potential as a long acting drug delivery platform for intravitreally injected drugs with reduced frequency of administration.