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Jimmy Hu, Roy S Chuck, Adam Friedman, Joel Friedman, Parimala Nacharaju, Mahatesh Navati, Wen-Jeng (Melissa) Yao, Cheng C Zhang, Jimmy Kyung Lee; Nanoparticles: A Novel Method of Intraocular Nitric Oxide Delivery. Invest. Ophthalmol. Vis. Sci. 2014;55(13):470.
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The ophthalmological translational potential of nitric oxide (NO) includes increasing retinal blood ﬂow in ischemic settings, lowering intraocular pressure in glaucoma, and combating infections. Here we report a novel method of sustained ocular NO delivery via a nanoparticle platform with established efficacy for both topical (non-ocular) and systemic applications.
NO-releasing nanoparticles (NO-np) were labeled with Alexafluor-594 and suspended 5mg/mL in balanced saline solution (BSS). Porcine whole globes were immersed in the suspension of fluorescent-labeled NO-np for 24 hours. Corneal penetration of NO-nps was determined by histological analysis of frozen sections. Additionally, porcine corneoscleral buttons were mounted onto an artificial anterior chamber and a 10 μM solution of diaminofluorescein-FM (DAF-FM, an indicator dye that increases in fluorescent intensity upon reaction with nitric oxide) in BSS was introduced into the anterior chamber. The external corneal surface was exposed to the NO-np suspension (5mg/mL in BSS) for 12 hours, after which the anterior chamber fluid was analyzed for fluorescence. DAF-FM mixed with NO-np suspension was used as a positive control. DAF-FM solution and NO-np suspension were used as negative controls.
Fluorescent labeled NO-nps were observed penetrating into the corneal stroma after incubation for 24 hours (see Fig 1). An increase in DAF-FM fluorescence was observed in the anterior chamber after 12 hours of exposure to NO-np to the corneal surface. The increase in DAF-FM fluorescent intensity gives evidence of NO penetration through corneal tissue (see Fig 2).
Nitric oxide’s vast range of therapeutic potential including increasing blood flow, lowering intraocular pressure, antimicrobial activity, and facilitating wound healing, has garnered much interest. However, its chemical instability and gaseous properties have limited its translation into clinical applications. Here, we demonstrate that a stable vehicle (NO-np) can be delivered through the cornea to release Nitric Oxide in the anterior chamber.
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