Ranibizumab biosimilar/polyethyleneglycol-conjugated gold nanoparticles as a novel drug delivery platform for age-related macular degeneration

Abstract

Ranibizumab is a first-line therapy against age-related macular degeneration. For further improvement of ranibizumab-based treatment, we developed ranibizumab biosimilar (Mab)/polyethyleneglycol (PEG)-conjugated small gold nanoparticles (core size: approximately 5 nm) as a novel platform of ranibizumab biosimilar (Mab) delivery. Mab/PEG-conjugated gold nanoparticles were successfully prepared, and the particles were characterized by transmission electron microscopy and dynamic light scattering method. The mean diameters of Mab/PEG-conjugated gold nanoparticles and PEG-conjugated gold nanoparticles were varied using different lengths of PEG chain (5 kDa and 10 kDa). The Mab conjugation efficiency was optimized by changing the amount of PEG in preparation, which showed a high conjugation efficiency (>70%). We found that Mab/PEG-conjugated gold nanoparticles effectively inhibited the tube formation of human umbilical vein endothelial cells based on Matrigel in vitro. PEG-conjugated gold nanoparticles without Mab inhibited the tube formation unexpectedly. The Mab/PEG-conjugated gold nanoparticles did not affect cell proliferation in human endothelial cells. These results suggest that Mab/PEG-conjugated gold nanoparticles can be used as a good and novel colloidal formulation against angiogenesis-related diseases in local sites such as age-related macular degeneration.