Abstract
Purpose :
Many ocular diseases leading to blindness are treated by intravitreal (IVT) injections. Frequent invasive ocular injections are associated to tolerability concerns, but perhaps more notably results in decreased treatment-compliance, ultimately worsening of vision. Reduction of IVT administration frequency by sustaining release of active ingredients through drug delivery systems (DDS) have failed due to poor tolerability. Our aim was to evaluate the intraocular tolerability of biodegradable non-porous silicon dioxide (silica) test items in a New Zealand White (NZW) rabbit study.
Methods :
Silica microparticles (MPs) were manufactured by sol-gel chemistry and spray drying and sterilized by gamma-irradiation. Silica MPs were mixed under aseptic conditions with either sterile silica hydrogel (HG) or endotoxin free water (ETFW) to form injectable silica MP-silica HG (depot) or MP suspensions (MPsusp), respectively. 24 NZW rabbits received IVT injections of depot ranging between 10-50µl via 27g ultra-thin wall needles and 8 received MPsusp at 50µl. Test items were evaluated up to 3 months via clinical observations, intra ocular pressure by non-contact tonometer (IOP), slit lamp exam (SLE) with 15 individual ocular safety and tolerability criteria, fundus imaging (FI), histolopathology (HP) of ocular tissues and aqueous humor and vitreous humor proteomics.
Results :
Observations by veterinarians showed no adverse events (AE) up to 3 months. IOP prior- and post-injection from 30 min to 1- and 3-months showed an increase in pressure upon dosing, returning to baseline within 30 min for both test items. SLE prior to injection and at days 3, 7, 16 and 1-, 2- and 3-months was used to assess features including lid margin and conjunctival redness, chemosis, optic nerve status, retinal status, lens status, implant location, anterior and posterior cells and flares as well as many more, finding no evidence of AE for any test item group up to 3 months. FI was conducted prior to dosing, immediately after dosing and at days 3, 7, 16 as well as at 1-, 2- and 3-months, with no AEs. HP and proteonomics were carried out at 1- and 3- months after dosing (pending).
Conclusions :
The results suggest that both silica MP-silica HG based depots and silica MP suspensions are well tolerated in rabbit eyes for durations currently up to 3 months at doses ranging from 10-50µl administered intravitreally.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.