DSP nanoparticles for treating nitrogen mustard induced corneal injury

PROJECT SUMMARY/ABSTRACT We aim to evaluate a novel approach for effective treatment of nitrogen mustard (NM)-induced corneal injury in rat and rabbit models. NM is a bi-functional analogue of sulphur mustard (SM). Ocular exposure of NM causes a range of complications including corneal ulceration, corneal opacity, chronic inflammation, corneal neovascularization, and even blindness. Therapeutic interventions to treat vesicants induced ocular injury has not been identified yet, which highlights the need to identify effective treatment options for vesicants-induced corneal injury. Dexamethasone sodium phosphate (DSP) eye drop is FDA approved drug for the treatment of ocular inflammation associated with various agents. Studies have reported beneficial effects of dexamethasone eye drops in vesicants-induced corneal injury in the rabbits. However, due to the rapid tear turnover and clearance of instilled drops and poor ocular bioavailability, frequent administration is necessary which results in poor patient compliance. To address these problems, we developed biodegradable nanoparticles of DSP with poly(lactic-co-glycolic acid) (PLGA) or poly(lactic acid) (PLA), that can be administered by subconjunctival (SCT) injection after NM exposure and provide sustained release of DSP, improving patient’s compliance and increasing therapeutic efficacy. We hypothesize that long-lasting PLA-DSP-NP (3 months in vitro drug release) could be effective in preventing corneal ulceration, corneal NV, corneal opacity, suppressing inflammatory and angiogenic biomarkers in both immediate (0 h post NM exposure) and delayed treatment (24 h post NM exposure). In Aim 1, we plan to investigate the dose-dependent efficacy of PLA-DSP-NP dosed at both 0 h and 24 h post NM exposure in the corneal injury rat model. In Aim 2, we will evaluate the efficacy of PLA-DSP-NP at a selected dose after immediate (0 h post NM exposure) and delayed treatment (24 h post NM exposure) in a more translational NM-induced corneal injury rabbit model.