Development of axitinib-loaded polymeric ocular implants for the treatment of posterior ocular diseases

Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are the primary causes of vision impairment and blindness worldwide. The current treatment for these diseases is an intravitreal injection of anti-VEGF agents, which are costly and require frequent injections. Implants can be used to sustain the release of drugs and minimize side effects. Axitinib (AX) is a potent VEGF receptor inhibitor and a promising candidate for treating posterior ocular diseases, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). A sustained release of AX was successfully achieved from 3D-printed AX-loaded implants fabricated using the well-known 3D printing technique, semi-solid extrusion (SSE). AX at concentrations of 10% w/w and 20% w/w was incorporated within the polycaprolactone (PCL) and Precirol®-based matrix. The fabricated implants were characterized via FTIR spectroscopy, SEM imaging, and thermal analysis. The implants were also evaluated for their drug release and biocompatibility. The AX-loaded implants exhibited thermal stability, and no chemical interactions were found between AX and the matrix components. The release mechanism study of AX revealed that the concentration of drug loading influenced AX release from the implant, with a 10% w/w and 20 %w/w of AX showing first-order and Korsmeyer-Peppas mechanism, respectively. A biocompatibility study using ARPE-19 cells confirmed that AX-loaded implants are nontoxic and safe for ocular use.