Topical application of insulin encapsulated by chitosan-modified PLGA nanoparticles to alleviate alkali burn-induced corneal neovascularization

Abstract

Corneal neovascularization (CRNV) severely impairs corneal transparency and is one of the leading causes of vision loss worldwide. Drug therapy is the main approach to inhibit CRNV. Insulin (INS) has been reported to facilitate the healing of corneal injuries and suppress inflammation. However, but due to the unique physiological barriers of the eye, its bioavailability is low, limiting its therapeutic effect. In this study, we developed a chitosan-poly(lactic-co-glycolic acid)-INS nanoparticles (CPI NPs) system for INS delivery. The characterization of CPI NPs was satisfactory. Experimental results demonstrated that CPI NPs effectively inhibited the migration of vascular endothelial cells and the formation of tubular structures. Furthermore, CPI NPs markedly suppressed the neovascularization in a CRNV model without any observable side effects. Quantitative proteomics analysis indicated that INS treatment led to a reduction in FTO levels within the neovascularized cornea. Both in vitro and in vivo experiments substantiated the impact of CPI NPs on FTO protein expression and the N6-methyladenosine modification. In conclusion, this study successfully developed an effective ocular drug delivery system for the treatment of CRNV induced by alkali burns, thereby offering a novel therapeutic option for this condition.