Abstract
Purpose :
Neovascular age-related macular degeneration (nAMD) and glaucoma are prevalent conditions that affect the posterior and anterior regions of the eye, respectively. nAMD treatment often necessitates monthly injections of anti-vascular endothelial growth factors (anti-VEGFs) and glaucoma often requires topical eye-drops to lower IOP. Sustained delivery of ocular therapeutics represents an opportunity to address unmet needs associated with these treatments. In nAMD, Tyrosine kinases inhibitors (TKIs) offer the ability to achieve pan-VEGF inhibition and, in glaucoma, beta-blockers achieve IOP lowering effects. This study investigates sustained axitinib and timolol delivery via polymeric implants using ethylene-vinyl acetate (EVA) for long-term (> 6 months) treatment.
Methods :
Axitinib-loaded implants (N=6) were made from milled EVA with 28% vinyl acetate at 50% drug loading. Timolol-loaded implants (N=6) were made from milled EVA 28% and 40% vinyl acetate and 10%, 40%, and 50% drug loading. Both groups were compounded via hot melt extrusion. Axitinib and timolol implants were weighed and placed into Eppendorf tubes with buffer solution (pH =7.4). Tween 80 (1%wt) or sodium lauryl sulfate (1%wt) was added to the axitinib implant buffer. The tubes were placed into incubators at 37 °C and 100 rpm. Samples were pulled over 28 days. UV-Vis spectroscopy and HPLC–UV were performed to quantify axitinib and timolol.
Results :
Axitinib was successfully compounded with 50% loading and formed into a cylindrical rod-implant shape. The 50%-loaded axitinib formulation achieved a cumulative release of 57 µg over 28 days. The 50%-loaded axitinib implants incubated with SLS-modified buffer demonstrated higher release (380 µg cumulative release) than the Tween 80 modified buffer (190 µg cumulative release). The 50% loaded formulations released timolol at a higher concentration when compared to 40% and 10% loaded formulations.
Conclusions :
This study demonstrates that the sustained release of axitinib and Timolol can be achieved using an EVA-based, monolithic implant design. This implant offers matrix drug release, and this design approach can be tuned to suit different implantation locations in the eye. The demonstrated 1-month release rate, in tandem with modeling, provides evidence that an EVA implant can deliver axitinib for greater than 6 months.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.