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.

Aiming at the disadvantages of easy recurrence of keratitis, difficult eradication by surgery, and easy bacterial resistance, insulin-loaded liposomes were prepared, and convolutional neural network was used as a statistical algorithm to build SD rat corneal inflammation model and study insulin-loaded liposomes, alleviating effect on corneal inflammatory structure in SD rats. The INS/PFOB@LIP was developed by means of thin-film dispersive phacoemulsification, its structure was monitored using a transmission electron microscope, particle size and appearance potential were monitored using a Malvern particle sizer, and ultraviolet consumption spectrum was monitored using a UV spectrophotometer. The encapsulation rate, drug loading, and distribution of insulin liposomes in rat corneal inflammatory model were measured and calculated. The cytotoxicity of liposome materials was evaluated by CCK-8 assay, and the toxic effects of insulin and insulin liposomes on cells were detected. The cornea of SD rats was burned with NaOH solution (1 mol/L), and the SD rat corneal inflammation model was created. The insulin liposome was applied to the corneal inflammation model, and the therapeutic effect of insulin liposome on corneal inflammation was evaluated by slit lamp, corneal immunohistochemistry, corneal HE staining, and corneal Sirius red staining. Insulin-loaded liposomes were successfully constructed with an average particle size of (130.69 ± 3.87) nm and a surface potential of (−38.24 ± 2.57) mV. The encapsulation rate of insulin liposomes was (48.89 ± 1.24)%, and the drug loading rate was (24.45 ± 1.24)%. The SD rat corneal inflammation model was successfully established. After insulin liposome treatment, the staining area of corneal fluorescein sodium was significantly reduced, the corneal epithelium was significantly thickened, the content of corneal collagen was increased, the expression of inflammatory factors was significantly reduced, and new blood vessels (corneal neovascularization, CNV) growth was inhibited.