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

Sagun Poudel; Ehsan Kaffash; Long Zhao; Rudra Pangeni; Woon Nam Chow; Qingguo Xu

doi:10.1016/j.exer.2024.109902

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

Exp Eye Res. 2024 Apr 18:243:109902. doi: 10.1016/j.exer.2024.109902. Online ahead of print.

Authors

Sagun Poudel¹, Ehsan Kaffash¹, Long Zhao¹, Rudra Pangeni¹, Woon Nam Chow², Qingguo Xu³

Affiliations

¹ Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, USA.
² Department of Ophthalmology, Virginia Commonwealth University, Richmond, VA 23298, USA; Department of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA.
³ Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, USA; Department of Ophthalmology, Virginia Commonwealth University, Richmond, VA 23298, USA; Center for Pharmaceutical Engineering, and Institute for Structural Biology, Drug Discovery & Development (ISB3D), Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA. Electronic address: qxu@vcu.edu.

PMID: 38641196
DOI: 10.1016/j.exer.2024.109902

Abstract

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.

Keywords: Corticosteroids; Dexamethasone; Ocular injury; PLGA; Subconjunctival injection; Vesicants.