Objective: The vascular endothelial growth factor (VEGF) family plays a pivotal role in controlling pathologic vascular angiogenesis and permeability in important eye diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Developing new therapy in addition to the conventional treatment such as laser photocoagulation to suppress VEGF-induced excessive retinal vascular permeability has emerged as a major research focus.
Methods and Results: In this study, we investigated the effect of HSA-PEG/Apatinib-a specific inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) using a murine model and human retinal microvascular endothelial cell line (HRMEC). Apatinib was efficiently loaded in HSA-PEG, a type of self-assembled nanostructures, which comprises of human serum albumin (HSA) and (poly)ethyleneglycol (PEG) to increase the solubility of water-insoluble drug, thus enhancing pharmacokinetics and bioavailability. To evaluate whether HSA-PEG/Apatinib could inhibit the VEGF-induced angiogenesis, the endothelial proliferation, tube formation and wounding migration were conducted. To assess vascular permeability, in vitro transendothelial resistance and paracellular permeability to dextran and in vivo leakage of intravenous FITC-labeled albumin and Evans blue dye into the retina were measured. Herein, we demonstrated that HSA-PEG/Apatinib significantly inhibited VEGF-induced angiogenesis and hyperpermeability in human retinal microvascular endothelial cells in vitro. In vivo, HSA-PEG/Apatinib significantly inhibited VEGF-mediated vascular leakage and diabetes-induced vascular breakdown in the retinal vessels.
Conclusion: Taken together, our findings showed that HSA-PEG/Apatinib could be a potential therapeutic treatment of VEGF-mediated retinal vascular angiogenesis and hyperpermeability in variable ocular diseases.
