RT Journal Article
SR Electronic
T1 Systemic anti-inflammatory therapy aided by double-headed nanoparticles in a canine model of acute intraocular inflammation
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eabb7878
DO 10.1126/sciadv.abb7878
VO 6
IS 35
A1 Ganugula, R.
A1 Arora, M.
A1 Lepiz, M. A.
A1 Niu, Y.
A1 Mallick, B. K.
A1 Pflugfelder, S. C.
A1 Scott, E. M.
A1 Kumar, M. N. V. Ravi
YR 2020
UL http://advances.sciencemag.org/content/6/35/eabb7878.abstract
AB 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-GA2-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-GA2-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-GA2 nanoparticles for systemic drug delivery across ocular barriers.