Anti-Vascular Endothelial Growth Factor Drug Conbercept-Loaded Peptide Hydrogel Reduced Angiogenesis in the Neovascular Age-Related Macular Degeneration.

Abstract

Age-related macular degeneration (AMD) accounts for 8.7% of the global blindness and neovascular form of AMD (nAMD) occupies a large proportion of severe visual loss and legal blindness caused by AMD with a relatively low incidence rate. Choroidal neovascularization (CNV) is overwhelmingly responsible for the occurrence of nAMD as bleeding and fluid leakage followed by abnormal formation of blood vessels could directly lead to loss of central vision so that reduce the choroidal angiogenesis is an ideal treatment method of nAMD. VEGF is an important cytokine which promote the signaling pathway of angiogenesis and the abnormal expression of VEGF is verified in great many CNV cases. Several anti-VEGF drugs have been widely used in clinical treatments such as ranibizumab, bevacizumab and aflibercept. Conbercept, as an originally developed drug in China, has attracted great attention. For the purpose of better treatment efficacy, our group designed a short chain peptide (Sequence: DDIIIRH-NH₂, M.W.880.99) for controlled drug release to remedy the drawback of the short half-time period. The peptide could self-assembled into a stable 'hydrogel under pH 7.4 condition and the 3D structure was clearly observed in TEM study. Rheological study exhibited its great injectability so that the hydrogel was a material for intravitreal injection. Statistics exhibited that the hydrogel could release approximately 50% of total conbercept. The In vitro experiments showed that either dose-dependent or the time-dependent incubation with peptide would not decrease the cell viability of HREC, revealing that the peptide was biocompatible. The most important is that co-incubation with HREC obviously reduced the HREC proliferation and tube formation induced by VEGF, ensuring its potential for the treatment efficacy of nAMD.