Citation24, Citation25 Variant kinds of nanoparticles such as liposome, gold nanoparticles, and polymeric nanoparticles were studied. Citation19 With a size lower than 1000 nm, not only the scratching and irritation of the eyes can be avoided when using nanoparticles, Citation22, Citation23 but the corneal permeability of drugs will also be enhanced. Nanoparticles (NPs) are distinct particulate systems with a size of 10–1000 nm and a specific surface charge. Citation19–21 These limitations have prompted researchers to develop new and effective drug delivery systems for eye treatment. Citation18, Citation19 Higher concentrations or repeated dosing is a way to overcome these limitations of drug administration, but these methods are not accurate due to a dramatic variation in the therapeutic concentration in the ocular tissue. However, a low bioavailability (<5%) of topical delivery due to various anatomical and physiological barriers, such as not allowing therapeutic agents to penetrate the corneal epithelium due to intracellular tight junctions, Citation17, Citation18 and constraints such as blinking and lacrimal draining have limited its applications. Citation15, Citation16 Compared with subconjunctival injection, topical therapy is the preferred method for patients because of the relatively safe and widely applicable approach. Citation14 Therefore, gp91 is considered a candidate for anti-angiogenic therapy.įor drug delivery to the eye, subconjunctival injection and topical therapy are the two feasible approaches. Citation11 Previous studies demonstrated that gp91ds-tat peptide (gp91) can mediate oxidative stress and reduce reactive oxygen species (ROS), Citation12, Citation13 which mediates many biological responses, including angiogenesis. For instance, blockade of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, especially NADPH oxidase 2 (Nox2), by gp91ds-tat peptide prevents diabetes-induced premature retinal endothelial cell senescence. Citation8–10 Thus, new compounds/drugs or formulas have also been developed for application in inhibiting vessel formation to effectively treat ocular NV. In addition to VEGF signaling, there are several other angiogenic factors are also known to be involved in ocular neovascularization. While anti-VEGF treatment is promising, partial efficacy, delivered in an invasive manner, resistance for longer treatment, and side effects have limited its clinical effect. Citation3, Citation7 Anti-VEGF treatment administered by topical, subconjunctival, and intraocular application is one of the major therapeutics used for ocular neovascularization treatment nowadays. Citation3, Citation5, Citation6 Several medical and surgical options have been used to treat corneal NV, such as laser ablation, photodynamic therapy, and anti-vascular endothelial growth factor (VEGF) treatment. Citation2–4 The mechanism underlying inflammation-induced NV results from the disruption of angiogenic and antiangiogenic balance in the cornea, which leads to significant corneal transparency change and visual impairment. Citation1 The increased permeability of these new vessels leads to chronic corneal edema, lipid exudation, inflammation, and scar formation. Citation1 Common causes of corneal neovascularization include chemical burns, trauma, contact lens wear, hypoxia, infection, corneal graft rejection, and immunological disease. Corneal neovascularization (NV) is a pathological condition of the cornea characterized by the invasion of new blood vessels into the avascular corneal regions from the limbus.
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