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

Abstract

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.

Ocular Nanomedicine

“…Oral administration of these nanoparticles in a canine model with lens-induced uveitis showed a notable drug level in aqueous humor and afforded protection against intraocular inflammation with reduced miosis, aqueous flare, and chemosis in the acute phase (<4 h) when compared with commercial anti-inflammatory treatment (oral carprofen) (Figure 12). [98] Excessive ROS is undoubtedly involved in the pathological origin of abnormal inflammatory responses during ocular inflammatory disorders, especially diabetic cataracts and AMD. Diabetic cataract is an ocular complication in patients with diabetes who often suffer from diminished visual function, and AMD is the leading cause of vision loss in elderly individuals with progressive photoreceptor death.…”

“…Reproduced with permission. [98] Copyright 2020, AAAS. nanosuspension of loteprednol etabonate, is delivered as mucuspenetrating particles coated with low molecular weight PEG.…”

“…Oral administration of these nanoparticles in a canine model with lens‐induced uveitis showed a notable drug level in aqueous humor and afforded protection against intraocular inflammation with reduced miosis, aqueous flare, and chemosis in the acute phase (<4 h) when compared with commercial anti‐inflammatory treatment (oral carprofen) ( Figure 12 ). [ 98 ]…”

“…TFA, trifluoroacetic acid; TREN, tris(2aminoethyl)amine; DIEA, N,N-diisopropylethylamine; EDC, 1-ethyl-3-(dimethylaminopropyl) carbodiimide. Reproduced with permission [98]. Copyright 2020, AAAS.…”

A Review of Ocular Drug Delivery Platforms and Drugs for Infectious and Noninfectious Uveitis: The Past, Present, and Future

“…Subconjunctival, controlled-release, carboxyl-poly lactic-co-glycolic acid, steroid-containing nanoparticles are also being optimized and have been shown to significantly reduce inflammation in rat models of uveitis [ 103 ]. Even systemically administered polyester nanoparticles loaded with curcumin, a potent anti-inflammatory extract, significantly reduced ocular inflammation in a lens-induced uveitis model [ 104 , 105 ]. Unfortunately, many of these aforementioned formulations of nanoparticles are in very preliminary stages of investigation and nanoparticle distribution and elimination in the eye are not well understood at this time [ 106 ].…”