Dexamethasone sodium phosphate loaded polymeric nanoparticles for treating nitrogen mustard induced corneal injury

Purpose : Nitrogen mustard (NM) is a potent vesicating chemical warfare agent that causes severe corneal injuries leading to inflammation, ulceration, neovascularization etc. Effective treatment therapies for vesicant-induced ocular injuries are not yet available. To address this potential threat, we engineered biodegradable polymeric nanoparticles (NPs) loaded with water-soluble dexamethasone sodium phosphate (DSP) or PLGA-DSP-NP. We aim to achieve sustained anti-inflammatory and anti-angiogenic effects for preventing NM-induced corneal injury following a single subconjunctival (SCT) injection. Methods : PLGA-DSP-NP was formulated using Poly (lactic-co-glycolic acid) (PLGA ) via a zinc ion bridge method. PLGA-DSP-NP was characterized for particle size, surface charge, morphology, drug loading and in vitro drug release profile. NM-induced corneal injury model was set up by exposing adult Sprague Dawley rats' eye with 1% NM for 1 minute. NM exposed rats were immediately treated with a single PLGA-DSP-NP SCT injection (180μg DSP) following NM exposure and followed for two weeks. As controls, NM treated rats with SCT injected DSP solution, saline, placebo NPs or DSP eyedrops were considered. Routine clinical observations and evaluations for corneal opacity, corneal ulceration, corneal neovascularization was performed till D14. mRNA expression level of inflammatory and angiogenic cytokines were quantified using qPCR at D14. Results : PLGA-DSP-NP had particle size of 250 ± 2.5 nm and surface charge of -3.6 ± 0.2 mV (Fig 1A). DSP-NP had 6.5 wt% drug loading and sustained in vitro drug release for two weeks (Fig 1B). NM exposed rats (1%, 1min) possessed significant ulceration (p