Abstract
Purpose : Nitrogen mustard (NM), a potent vesicant, causes severe corneal injuries with no FDA-approved treatments. Peroxisome proliferator-activated receptor α (PPARα) is highly expressed in the cornea, and its protein level is reduced after NM injury. Activating PPARα may be a promising therapeutic strategy for NM-induced corneal injury. This study aimed to develop a new microemulsion eyedrop of the PPARα agonist fenofibrate and to evaluate its efficacy in a rat model of NM-induced corneal injury.
Methods : Microemulsion eyedrops containing 0.5% fenofibrate were prepared with 3% oil, 15% emulsifier, and 7.5% co-emulsifier. The formulation was characterized for droplet size/distribution, surface charge, viscosity, tonicity, and drug loading. Blink rate, intraocular pressure (IOP), and tear secretion were monitored in healthy rats after TID dosing. Therapeutic efficacy was tested in an NM-induced corneal injury model in SD rats, generated by applying a 1% NM–soaked filter paper to the cornea for 2 min. Treatment started 1 h after injury with 0.5% fenofibrate microemulsion (TID, n=10-14 eyes/group) for 14 days with placebo microemulsion and saline as controls. Corneal opacity, ulceration, and neovascularization were clinically scored, and corneas were collected at day 14 for histological analysis.
Results : Microemulsion eyedrops had ~20 nm droplets (PDI < 0.1), near-neutral charge (-0.7 mV), and >95% drug loading. The formulation was shear-thinning and retained high viscosity at 35°C (134.5 mPa.s). No ocular toxicity or irritation was observed after 7 days of dosing in healthy rats. In NM-injured corneas, 0.5% fenofibrate microemulsion significantly reduced ulceration (1.2-fold vs saline, P<0.05; 1.3-fold vs placebo, P<0.01), neovascularization (2.3-fold vs saline, 1.9-fold vs placebo; both P<0.001), and opacity (1.6-fold vs saline, P<0.001; 1.5-fold vs placebo, P<0.01) over 14 days. Histology showed that NM-injured corneas treated by microemulsion eyedrop had significantly reduced epithelial degradation (P<0.001) and 15-20% lower total corneal thickness in comparison to saline (P<0.01) and placebo (P<0.05), whereas saline and placebo treated corneas exhibited epithelial loss with extensive stromal inflammation.
Conclusions : The microemulsion eyedrop containing fenofibrate may become a promising therapy for the corneal injuries induced by vesicants.
Methods : Microemulsion eyedrops containing 0.5% fenofibrate were prepared with 3% oil, 15% emulsifier, and 7.5% co-emulsifier. The formulation was characterized for droplet size/distribution, surface charge, viscosity, tonicity, and drug loading. Blink rate, intraocular pressure (IOP), and tear secretion were monitored in healthy rats after TID dosing. Therapeutic efficacy was tested in an NM-induced corneal injury model in SD rats, generated by applying a 1% NM–soaked filter paper to the cornea for 2 min. Treatment started 1 h after injury with 0.5% fenofibrate microemulsion (TID, n=10-14 eyes/group) for 14 days with placebo microemulsion and saline as controls. Corneal opacity, ulceration, and neovascularization were clinically scored, and corneas were collected at day 14 for histological analysis.
Results : Microemulsion eyedrops had ~20 nm droplets (PDI < 0.1), near-neutral charge (-0.7 mV), and >95% drug loading. The formulation was shear-thinning and retained high viscosity at 35°C (134.5 mPa.s). No ocular toxicity or irritation was observed after 7 days of dosing in healthy rats. In NM-injured corneas, 0.5% fenofibrate microemulsion significantly reduced ulceration (1.2-fold vs saline, P<0.05; 1.3-fold vs placebo, P<0.01), neovascularization (2.3-fold vs saline, 1.9-fold vs placebo; both P<0.001), and opacity (1.6-fold vs saline, P<0.001; 1.5-fold vs placebo, P<0.01) over 14 days. Histology showed that NM-injured corneas treated by microemulsion eyedrop had significantly reduced epithelial degradation (P<0.001) and 15-20% lower total corneal thickness in comparison to saline (P<0.01) and placebo (P<0.05), whereas saline and placebo treated corneas exhibited epithelial loss with extensive stromal inflammation.
Conclusions : The microemulsion eyedrop containing fenofibrate may become a promising therapy for the corneal injuries induced by vesicants.
| Original language | American English |
|---|---|
| Pages (from-to) | 2945 |
| Journal | Investigative Ophthalmology and Visual Science |
| Volume | 67 |
| State | Published - Jun 2026 |
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