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GA Fischer, D Vollmer, M Szlek, T Plummer; Transscleral Iontophoretic Delivery of a Model Anionic Drug to Rabbit Eyes: A Reproducibility Study . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2323.
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Purpose: The study objectives were (1) to determine the amount and distribution of a model anionic drug, diclofenac, delivered to rabbit eyes following transscleral iontophoresis and (2) to determine the inter-study reproducibility of the amount and distribution. Methods: For reproducibility experiments, three separate studies each comprised of four groups (n=6) of New Zealand White rabbits were treated with a 7-mg/mL aqueous diclofenac solution at 0, 2, 3 or 4 mA of current for twenty minutes. An ocular rabbit applicator composed of an 170-µL silicone shell (backed with Ag/AgCl-coated Ag foil and containing a single layer of a hydrogel-impregnated polyvinyl acetal matrix) was used. The applicator was placed against the rabbit's eye in the upper cul-de-sac at the limbus with the front edge 1-2 mm distal from the corneoscleral junction. Following treatment, the rabbits were euthanized, the eyes enucleated and then frozen at -70 °C. The eyes were dissected into the following tissues: vitreous humor, anterior segment, cornea, sclera, and choroid/retina. Tissues were analyzed by using 14C-radiolabel diclofenac. Results: The total amount of drug for all three studies delivered in the 0-, 2-, 3-, and 4-mA treatment groups was 2.0 ± 0.8, 6.7 ± 0.8, 9.6 ± 1.6, and 14.1 ± 2.3 µg, respectively. Most of the drug was found in the treated portion of the sclera (40-67%) and lesser, but still therapeutic amounts, in the retina/choroid (3-6%). The data also demonstrate a transport dependence with respect to current. Conclusions: Anionic drug delivery to the eye is enhanced with transscleral iontophoresis; enhancement is 15-fold to the retina/choroid tissue. Iontophoresis offers a non-invasive and reproducible means of delivering therapeutic levels of a model anionic drug.
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