Bevacizumab-polymer conjugate for enhanced stability and anti-angiogenic activity

Pathological angiogenesis is a central mechanism underlying age-related macular degeneration (AMD), one of the leading causes of irreversible vision loss worldwide. Abnormal vascular growth in the retina induces leakage, inflammation and progressive degeneration of photoreceptors. Current treatment strategies primarily rely on intravitreal administration of antibody for inhibition of vascular epithelial growth factor (VEGF). Anti-VEGF antibody suppresses neovascularization, but repeated injections are often required to maintain therapeutic efficacy. This leads to risks of ocular tissue damage and considerable patient burden. To overcome these limitations, we developed a bevacizumab-poloxamer conjugate (BPX) aimed at improving intraocular stability and therapeutic efficacy. Poloxamer, an amphiphilic and clinically approved polymer, was covalently conjugated to bevacizumab (BEV) to exploit its protein stabilizing property. BPX preserved the structural integrity of the native BEV, while demonstrating enhanced resistance against various conditions. Additionally, BPX exhibited superior inhibition of angiogenesis compared with the native BEV, as demonstrated in cellular level and ex vivo model. These results suggest that poloxamer conjugation to antibody offers a promising approach to improve the efficacy and convenience of anti-VEGF treatment for AMD.