Systemic anti-inflammatory therapy aided by double-headed nanoparticles in a canine model of acute intraocular inflammation

摘要

Novel approaches circumventing blood-ocular barriers in systemic drug delivery are lacking. We hypothesize receptor-mediated delivery of curcumin (CUR) across intestinal and ocular barriers leads to decreased inflammation in a model of lens-induced uveitis. CUR was encapsulated in double-headed polyester nanoparticles using gambogic acid (GA)–coupled polylactide-co-glycolide (PLGA). Orally administered PLGA-GAsub2/sub-CUR led to notable aqueous humor CUR levels and was dosed (10 mg/kg twice daily) to adult male beagles ( n = 8 eyes) with induced ocular inflammation. Eyes were evaluated using a semiquantitative preclinical ocular toxicology scoring (SPOTS) and compared to commercial anti-inflammatory treatment (oral carprofen 2.2 mg/kg twice daily) ( n = 8) and untreated controls ( n = 8). PLGA-GAsub2/sub-CUR offered improved protection compared with untreated controls and similar protection compared with carprofen, with reduced aqueous flare, miosis, and chemosis in the acute phase (4 hours). This study highlights the potential of PLGA-GAsub2/sub nanoparticles for systemic drug delivery across ocular barriers.