Ferrostatin‐1‐loaded liposome for treatment of corneal alkali burn via targeting ferroptosis

Abstract

Alkali burn is a potentially blinding corneal injury. During the progression of alkali burn‐induced injury, overwhelmed oxidative stress in the cornea triggers cell damage, including oxidative changes in cellular macromolecules and lipid peroxidation in membranes, leading to impaired corneal transparency, decreased vision, or even blindness. In this study, we identified that ferroptosis, a type of lipid peroxidation‐dependent cell death, mediated alkali burn‐induced corneal injury. Ferroptosis‐targeting therapy protected the cornea from cell damage and neovascularization. However, the specific ferroptosis inhibitor ferrostatin‐1 (Fer‐1) is hydrophobic and cannot be directly applied in the clinic. Therefore, we developed Fer‐1‐loaded liposomes (Fer‐1‐NPs) to improve the bioavailability of Fer‐1. Our study demonstrated that Fer‐1‐NPs exerted remarkable curative effects regarding corneal opacity and neovascularization in vivo. The efficacy was comparable to that of dexamethasone, but without appreciable side effects. The significant suppression of ferroptosis (induced by lipid peroxidation and mitochondria disruption), inflammation, and neovascularization might be the mechanisms underlying the therapeutic effect of Fer‐1‐NPs. Moreover, the Fer‐1‐NPs treatment showed no signs of cytotoxicity, hematologic toxicity, or visceral organ damage, which further confirmed the biocompatibility. Overall, Fer‐1‐NPs provide a new prospect for safe and effective therapy for corneal alkali burn.

Identification of potential ferroptosis-related biomarkers and a pharmacological compound in diabetic retinopathy based on machine learning and molecular docking

“…DR, characterized by ischemic microvascular disease of the retina and retinal neurodegeneration, is a highly specific complication of diabetes with complex multifactorial pathophysiology, which finally leads to visual impairment or blindness (29). Emerging evidence from a series of in vivo and in vitro studies revealed that ferroptosis, a new type of irondependent programmed cell death linking metabolism, disease, immune cells, and targeted therapy, is closely associated with the pathophysiological states of various ocular diseases, such as corneal alkali burn, glaucoma, age-related macular degeneration, and retinitis pigmentosa (6,(30)(31)(32). Furthermore, targeting ferroptosis is a promising treatment for ocular diseases (6,31).…”

Anti‐Oxidative and Anti‐Inflammatory Micelles: Break the Dry Eye Vicious Cycle

“…Losmapimod (Los) is a safe and well‐tolerated p38 MAPK inhibitor that shows remarkable inhibiting effects in cardiological, pulmonary, and neural clinical experiments. [ 29 , 30 , 31 ] Based on the potency of Tem and Los for resolution of inflammation and our existing expertise in nanocarriers for ocular surface drug delivery, [ 32 , 33 , 34 ] we developed a novel, safe, and highly effective micellar eye drops that mainly consist of the Los‐loaded and Tem‐conjugated cationic polypeptide micelles, MTem/Los, for the superior combat against DED vicious cycle ( Figure 1 a ). The MTem/Los micelles were prepared simply by the self‐assembly of cationic Tem‐conjugated polypeptides with the Los package.…”

Cancer-Associated Fibroblast-Targeted Delivery of Captopril to Overcome Penetration Obstacles for Enhanced Pancreatic Cancer Therapy

“…A film-ultrasonic dispersion method was used to prepare captopril loaded CAFs-targeted liposomes (FH-Lip-Cap). , In brief, a mixture of lipids (30 mg) containing phospholipids (A.V.T, PC98T, N01001), cholesterol (A.V.T, O01001), and DSPE-mPEG 2000 (A.V.T, F01008) was dissolved in dichloromethane at a mole ratio of 20:10:1 (10 mL, DCM). Vacuum rotary evaporator was used to dry the DCM solvent and prepare a thin lipid film at a 50 mL flask.…”