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E. Eljarrat–Binstock, F. Orucov, J. Frucht–Pery, J. Pe'er, A.J. Domb; Methotrexate Delivery to Posterior Segments of the Eye Using Transscleral Hydrogel–Iontophoresis . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2821.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate methotrexate (MTX) penetration to posterior segments of the eye after a short and low current transscleral iontophoresis, using drug–loaded hydrogel mounted on a portable iontophoretic device.
Iontophoresis of methotrexate was studied in healthy white rabbits using drug–loaded disposable hydrogel sponges mounted on a portable iontophoretic device. Cylindrical hydrogel sponges (0.5cm in diameter) containing an average amount of 10.6mg methotrexate were used. Transscleral iontophoresis was performed with a current intensity of 1 mA (5mA/cm2) for 5 min on the pars–plana area, while the complementary electrode (anode) was attached to the ear of the rabbit. The experimental settings included two control groups (8 eyes each): mock iontophoresis (no current application) for 5 minutes and intravitreal injection of 400mcg MTX. Two hours after treatment animals were sacrificed and eyes were dissected. Methotrexate levels in different segments of the eye were determined using a fluorescence polarization immunoassay by TDx System Analyzer (Abbott Laboratories, Abbott Park, IL, USA).
Significantly higher drug levels were found in the sclera, retina and vitreous after transscleral iontophoresis of 5 minutes compared with the control group of mock iontophoresis (194.0±148.0µg/g, 38.6±19.5µg/g and 0.18±0.13µg/ml respectively). Methotrexate concentrations after a single iontophoresis treatment were approximately four and three–folds higher compared to those obtained after mock iontophoresis, in the sclera and vitreous, respectively and twice higher in the retina. Methotrexate concentrations in the retina, vitreous and aqueous humor two hours after intravitreal injection were extremely high compared to the iontophoretic group (607.1, 176.6 and 11.5 µg/g, respectively).
A short low current non–invasive iontophoretic treatment using methotrexate–loaded hydrogels has a potential clinical value in treating ocular posterior segment inflammatory disease and intraocular lymphoma, by increasing drug penetration to the eye and maintaining therapeutic levels.
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