A novel therapy to ameliorate nitrogen mustard-induced limbal stem cell deficiency using lipoprotein-like nanoparticles.

Abstract

Chronic corneal inflammation, a component of sulfur mustard (SM) and nitrogen mustard (NM) injuries frequently leads to limbal stem cell deficiency (LSCD), which can compromise vision. Corneal conjunctivalization, neovascularization, and persistent inflammation are hallmarks of LSCD. Ocular exposure to SM and NM results in an acute and delayed phase of corneal disruption, culminating in LSCD. Available therapies for mustard keratopathy (e.g., topical corticosteroids) often have adverse side effects, and generally are ineffective in preventing the development of LSCD. We developed a novel, optically transparent HDL nanoparticle (NP) with an organic core (oc) molecular scaffold. This unique oc-HDL NP: (i) markedly improved corneal haze during the acute and delayed phases in vivo; (ii) significantly reduced the inflammatory response; and (iii) blunted conjunctivalization and corneal neovascularization during the delayed phase. These findings strongly suggest that our HDL NP is an ideal treatment for mustard keratopathy and other chronic corneal inflammatory diseases.