Inhibiting corneal neovascularization by sustainably releasing anti-VEGF and anti-inflammation drugs from silica-thermogel nanohybrids

Abstract

Corneal neovascularization (CNV) is one of the main factors that induce blindness worldwide. To effectively inhibit CNV, a novel nanohybrid has been developed by incorporating anti-VEGF bevacizumab (BEV)-loaded mesoporous silica nanoparticles (BEV@MSN) into the thermogel matrix with anti-inflammation cyclosporine A (CsA) (BEV@MSN-CsA@Thermogel). This nanohybrid regulates the in vitro release of both bevacizumab and cyclosporine A in a sustainable way for up to four weeks to enhance CNV inhibition through the synergistic anti-VEGF and anti-inflammation. The carrier materials (i.e. silica and thermogel) in this nanohybrid do not show any cytotoxicity to human Tenon's fibroblasts, corneal epithelial cells and corneal endothelial cells. BEV@MSN-CsA@Thermogel effectively prevents proliferation, migration, and tube-like structure formation of human umbilical vein endothelial cells. Moreover, subconjunctival injection of BEV@MSN-CsA@Thermogel significantly inhibits corneal neovascularization in terms of the CNV area, the new vessel length, the corneal opaque area, the corneal inflammation and abnormal fibrosis in a rabbit model. This nanohybrid is thus a promising alternative for effective CNV treatment.

Keywords: Corneal neovascularization; Mesoporous silica nanoparticle; Nanohybrid; Synergistic treatment; Thermogel.