Abstract
Purpose :
Age related macular degeneration (AMD) is a leading cause of visual impairment and blindness in the world. Treatment of Neovascular AMD, caused by choroidal neovascularization and vascular leakage, requires monthly injections of anti-vascular endothelial growth factors (anti-VEGFs) which can cause endophthalmitis or retinal detachment in some patients. Additionally, the monthly dosing frequency represents a significant treatment burden for patients. Sustained release of therapeutics for AMD via a polymeric implant represents an opportunity to overcome high treatment burden and may mitigate some safety concerns. This study investigates the sustained release of axitinib (a tyrosine kinase inhibitor) via ethylene-vinyl acetate (EVA) polymeric implants in simulated vitreous humor.
Methods :
28% vinyl acetate EVA was cryo-milled to achieve smaller particle size. The resultant EVA was mixed with 50% axitinib and compounded via a hot melt extrusion process. Axitinib loaded implants were produced in cylindrical rod shapes. Implants were weighed and placed into Eppendorf tubes with various buffer solutions: solution A (PBS buffer pH 7.4), solution B (pH 7.4 PBS with 1% Tween 80) and solution C (simulated vitreous humor). The tubes were placed into incubators at 37 °C and 100 rpm. Elution media was pulled over 35 days. HPLC–UV was performed to quantify axitinib release.
Results :
Axitinib was successfully compounded with and formed into a cylindrical rod-implant shape with 0.4 - 0.5 mm diameter and 5 mm length. The 50%-loaded axitinib formulation achieved a cumulative release of 3.6 µg over 35 days in PBS buffer solution. However, the 50%-loaded axitinib implants incubated with simulated vitreous humor demonstrated higher cumulative release of 6.4 µg over 35 days. Implants in the PBS and 1% Tween80 buffer demonstrated the highest release of 28.8 µg over 35 days.
Conclusions :
This study demonstrates hot melt extrusion technology can be utilized to produce 50% axitinib loaded EVA retinal implants. Axitinib release from the implants was influenced by buffer conditions with simulated vitreous humor showing 77% higher release than implants in the PBS buffer solution. The demonstrated 1-month release rate, in tandem with modeling, provides evidence that an EVA implant can deliver axitinib for greater than 6 months in therapeutically relevant amounts.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.