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A. C. Amrite, E. R. Escobar, G. Goel, H. F. Edelhauser, U. B. Kompella; Sub-50-nm Nanoparticles: Ocular Distribution in an ex vivo Eye Model and Transscleral Transport. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5806.
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One objective of this study was to determine the distribution of sub-50-nm nanoparticles after topical, intra-stromal, and intra-cameral modes of administration. Another objective was to assess the transscleral transport of the nanoparticles.
In an ex vivo bovine eye model, 20-nm anionic Fluosphere® (hydrodynamic diameter: 45 nm) suspension was administered as an eye drop (1 mg/ml; 50µl) or as an injection into the stroma (1 mg/ml; 10 µl) or aqueous humor (10 mg/ml; 50 µl). At 1 hr post-dosing, various tissues including the corneal epithelium, stroma, endothelium, aqueous humor, ciliary body, lens, vitreous humor, retina, choroid, and sclera were isolated and particles were extracted and quantified by spectrofluorometry. Further, permeability of nanoparticles across isolated bovine sclera and sclera-choroid-RPE was assessed up to 24 hrs and the sclera was visualized with confocal microscopy.
The concentrations in tissues with quantifiable particle levels exhibited the following trends. Eye drop: corneal epithelium > stroma > endothelium; Intra-stromal injection: stroma > epithelium; Intra-cameral injection: aqueous humor > endothelium. The nanoparticle levels in other tissues were negligible. After intra-stromal and intra-cameral injections, most of the dose was accounted for in the stroma (66 ± 23%) and aqueous humor (65 ± 34%), respectively. With eye drop, only 2.4% of the dose could be accounted for in the cornea. Removal of epithelium enhanced corneal nanoparticle delivery from eye drops to ~23%. With the three routes of administration, nanoparticle delivery to the cornea was in the order: intra-stromal > topical > intra-cameral. The cumulative nanoparticle transport at 24 hr across sclera-choroid-RPE was below detection limits and that across sclera was 0.46 ± 0.064%.
Delivery of nanoparticles to the posterior segment is insignificant following topical, intra-stromal, or intra-cameral administrations. Corneal epithelium, corneal endothelium, and choroid-RPE are significant barriers for nanoparticle delivery. Also, thick matrix tissues such as stroma and sclera significantly hinder nanoparticle diffusion.
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