Dexamethasone sodium phosphate loaded nanoparticles for prevention of nitrogen mustard induced corneal injury

• Published in: Experimental eye research 2024-06, Vol.243, p.109902, Article 109902
• Main Authors: Poudel, Sagun, Kaffash, Ehsan, Zhao, Long, Pangeni, Rudra, Chow, Woon Nam, Xu, Qingguo
• Format: Article
• Language: English
• Subjects: Animals; Burns, Chemical - drug therapy; Burns, Chemical - prevention & control; Chemical Warfare Agents - toxicity; Cornea - drug effects; Cornea - metabolism; Cornea - pathology; Corneal Injuries - chemically induced; Corneal Injuries - drug therapy; Corneal Injuries - pathology; Corneal Injuries - prevention & control; Corticosteroids; Dexamethasone; Dexamethasone - analogs & derivatives; Disease Models, Animal; Eye Burns - chemically induced; Eye Burns - prevention & control; Glucocorticoids; Mechlorethamine - toxicity; Mice; Nanoparticles; Ocular injury; PLGA; Rabbits; Subconjunctival injection; Vesicants
• ISSN: 0014-4835; 1096-0007; 1096-0007
• DOI: 10.1016/j.exer.2024.109902

Nitrogen mustard (NM) is a potent vesicating chemical warfare agent that is primarily absorbed through skin, inhalation, or ocular surface. Ocular exposure of NM can cause acute to chronic keratopathy which can eventually lead to blindness. There is a current lack of effective countermeasures against ocular exposure of NM despite their imperative need. Herein, we aim to explore the sustained effect of Dexamethasone sodium phosphate (DSP)-loaded polymeric nanoparticles (PLGA-DSP-NP) following a single subconjunctival injection in the management and prevention of corneal injury progression upon exposure to NM. DSP is an FDA approved corticosteroid with proven anti-inflammatory properties. We formulated PLGA-DSP-NP with zinc chelation ion bridging method using PLGA polymer, with particles of approximately 250 nm and a drug loading of 6.5 wt%. Under in vitro sink conditions, PLGA-DSP-NP exhibited a sustained drug release for two weeks. Notably, in NM injured cornea, a single subconjunctival (SCT) injection of PLGA-DSP-NP outperformed DSP eyedrops (0.1%), DSP solution, placebo NP, and saline, significantly mitigating corneal neovascularization, ulceration, and opacity for the two weeks study period. Through PLGA-DSP-NP injection, sustained DSP release hindered inflammatory cytokine recruitment, angiogenic factors, and endothelial cell proliferation in the cornea. This strategy presents a promising localized corticosteroid delivery system to effectively combat NM-induced corneal injury, offering insights into managing vesicant exposure. [Display omitted] •Nitrogen mustard exposure causes corneal ulceration, opacity, and neovascularization.•Nitrogen mustard exposure upregulates multiple inflammatory and angiogenic cytokines in the cornea.•A single subconjunctival (SCT) injection of PLGA-DSP-NP prevents the progression of NM-induced corneal injury.