Liposome–trimethyl chitosan nanoparticles codeliver insulin and siVEGF to treat corneal alkali burns by inhibiting ferroptosis

Abstract

Alkali burns are potentially blinding corneal injuries. Due to the lack of available effective therapies, the prognosis is poor. Thus, effective treatment methods for corneal alkali burns are urgently needed. Codelivery nanoparticles (NPs) with characteristics such as high bioavailability and few side effects have been considered effective therapeutic agents for ocular diseases. In this study, we designed a new combination therapy using liposomes and trimethyl chitosan (TMC) for the codelivery of insulin (INS) and vascular endothelial growth factor small interfering RNA (siVEGF) to treat alkali-burned corneas. We describe the preparation and characterization of siVEGF-TMC-INS-liposome (siVEGF-TIL), drug release characteristics, intraocular tracing, pharmacodynamics, and biosafety. We found that siVEGF-TIL could inhibit oxidative stress, inflammation, and the expression of VEGF in vitro and effectively maintained corneal transparency, accelerated epithelialization, and inhibited corneal neovascularization (CNV) in vivo. Morever, we found that the therapeutic mechanism of siVEGF-TIL is possibly relevant to the inhibition of the ferroptosis signaling pathway by metabolomic analysis. In general, siVEGF-TIL NPs could be a safe and effective therapy for corneal alkali burn.

Ferroptosis: a novel mechanism of cell death in ophthalmic conditions

“…The collective findings from these studies highlight the critical role of ferroptosis in corneal injury and suggest that its inhibition could be beneficial for corneal preservation ( 152 , 232 ). The development of pharmaceuticals based on the understanding of ferroptosis offers promising avenues for treating corneal injuries ( 233 ).…”

The Role of Insulin-like Growth Factor (IGF) System in the Corneal Epithelium Homeostasis—From Limbal Epithelial Stem Cells to Therapeutic Applications

“…Recently, a convolutional neural network statistical analysis was applied to demonstrate the therapeutic effect of insulin liposomes on corneal epithelial defects in rats [ 120 ]. In a study of alkali-burned corneal models, a nano-system combining liposomes and trimethyl chitosan was used to deliver insulin and vascular endothelial growth factor small interfering RNA [ 121 ]. This combined therapy proved effective in reducing oxidative stress, increasing epithelialization, and inhibiting corneal neovascularization.…”