Design and evaluation of semi-solid lipid implants for controlled intravitreal release of bevacizumab.

Bevacizumab is a monoclonal antibody used intravitreally as an anti-VEGF therapy for some ocular diseases. However, this type of treatment presents some limitations, such as the invasiveness of its administration and the need for frequent injections due to the clearance of the antibody from the vitreous chamber. Semi-solid lipid implants emerge as an attractive possibility for the sustained release of biological drugs like bevacizumab, so they could have great potential for the subsequent treatment of VEGF-dependent degenerative retinal pathologies, such as proliferative diabetic retinopathy or neovascular age-related macular degeneration. In this work, injectable lipid implants were designed based on the lipids Precirol® ATO 5, Tefose® 63, GeleolTM, and Tefose® 1500. The implants were easy to manufacture by melting and mixing. The surface of the implants was characterized by scanning electron microscopy, while the distribution of bevacizumab inside was characterized by confocal Raman mapping microscopy. Subsequently, the state of the antibody after release was evaluated by Raman Spectroscopy and Attenuated Total Reflection Infrared spectroscopy, showing an unaltered quaternary structure. Furthermore, the implants were able to sustain the antibody release for almost 40 days. Biocompatibility was assessed by assay with ARPE-19 cells. Finally, the calorimetry assay allowed us to refine the best possible formulation for further studies. This type of implant showed suitable properties as a potential therapeutic platform for the treatment of neovascular age-related macular degeneration and proliferative diabetic retinopathy, being injectable, easy to make, homogeneous, having sustained release and being biocompatible.