title: Hydrogel probe for iontophoresis drug delivery to the eye.
abstract: The aim of this study was to evaluate the use of a solid hydrogel loaded with a drug solution as a probe for ejecting drugs to the eye upon application of low current iontophoresis. Hydroxyethyl methacrylate (HEMA), cross-linked with ethylene glycol dimethacrylate (EGDMA), and cross-linked arabinogalactan or dextran were prepared to form solid hydrogels. The hydrogels were examined for their mechanical suitability, absorption of drug solution and in vitro release properties when applying an iontophoretic current through the drug-loaded hydrogel into a solid-agar surface. Transconjunctival and transscleral iontophoresis of gentamicin sulfate was studied in healthy rabbits using drug-loaded disposable HEMA hydrogel disc probes. Gentamicin concentrations in different eye segments were assayed using a fluorescence polarization immunoassay. Preliminary corneal toxicity was examined in rabbits using a current intensity of 2.5 and 5.1 mA/cm2 for 60 and 120 s. The most appropriate hydrogel is composed of HEMA, 2% EGDMA and 75% water. lontophoresis onto agar gel was found indicative for the evaluation of iontophoretic activity of a hydrogel. Transscleral iontophoretic treatment resulted in high concentrations of drugs in the posterior segments of the eye. Application of iontophoresis onto the rabbit eye caused a reversible swelling of the cornea which lasted a few hours after application. Low current iontophoresis using drug-loaded hydrogel has a potential clinical value in obtaining high drug concentration at posterior segments of the eye.
authors.affiliation: Department of Medicinal Chemistry and Natural Products, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Esther
authors.initials: E
authors.lastname: Eljarrat-Binstock
authors.forename: Frederik
authors.initials: F
authors.lastname: Raiskup
authors.forename: Joseph
authors.initials: J
authors.lastname: Frucht-Pery
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Domb
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003911:Dextrans; D004337:Drug Carriers / Q000737:chemistry*; D005123:Eye / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005128:Eye Diseases / Q000188:drug therapy; D005685:Galactans; D005839:Gentamicins / Q000008:administration & dosage / Q000493:pharmacokinetics; D020100:Hydrogels / Q000737:chemistry / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy; D007478:Iontophoresis / Q000009:adverse effects / Q000379:methods; D008689:Methacrylates; D011817:Rabbits; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D003911:Dextrans; D004337:Drug Carriers; D005685:Galactans; D005839:Gentamicins; D020100:Hydrogels; D008689:Methacrylates; C005044:hydroxyethyl methacrylate; C004919:ethylene dimethacrylate; C005653:arabinogalactan