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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\u2010burned corneas. We describe the preparation and characterization of siVEGF\u2010TMC\u2010INS\u2010liposome (siVEGF\u2010TIL), drug release characteristics, intraocular tracing, pharmacodynamics, and biosafety. We found that siVEGF\u2010TIL 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\u2010TIL is possibly relevant to the inhibition of the ferroptosis signaling pathway by metabolomic analysis. In general, siVEGF\u2010TIL NPs could be a safe and effective therapy for corneal alkali burn.<\/jats:p>","DOI":"10.1002\/btm2.10499","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T03:57:04Z","timestamp":1675915024000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["<scp>Liposome\u2013trimethyl<\/scp>\n                    chitosan nanoparticles codeliver insulin and\n                    <scp>siVEGF<\/scp>\n                    to treat corneal alkali burns by inhibiting ferroptosis"],"prefix":"10.1002","volume":"8","author":[{"given":"Xiaojing","family":"Xiong","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Second Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of Ultrasound Molecular Imaging Second Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"State Key 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