title: Iontophoresis-gentamicin delivery into the rabbit cornea, using a hydrogel delivery probe.
abstract: OBJECTIVE
  To evaluate the efficacy of penetration of gentamicin into the cornea of rabbits using iontophoresis with a hydrogel-gentamicin containing probe.
  
  
  METHODS
  Eight of 10 groups (groups 3-10) of 6 rabbits (one eye per rabbit), underwent corneal iontophoresis using soft stable hydroxyethyl methacrylate hydrogel discs (80% water content) loaded with gentamicin sulphate which were mounted on an iontophoresis probe. The studied current intensities were 0, 0.1, 0.3 and 0.6 mAmp, and the durations of iontophoresis were 10 and 60 sec. Two control groups received 1.4% topical drops of gentamicin every 5 min for 1 hr (group 1) or sub-conjunctival injection of 10 mg gentamicin (group 2). Following sacrifice, aqueous humour was taken, corneas were excised, and gentamicin concentration was determined in aqueous humour and cornea samples.
  
  
  RESULTS
  Post-iontophoresis, the concentration of gentamicin in the corneas ranged from high (88.60 +/- 38.64 microg ml(-1)) to very low (0.10 +/- 0.89 microg ml(-1)). Both the control groups and those rabbits treated with current intensity of 0.1 mAmp or greater obtained therapeutic gentamicin levels in the corneas. Use of iontophoresis for 60 sec or current intensity greater than 0.1 mAmp obtained corneal gentamicin levels not different from sub-conjunctival injection. Application of current intensity of 0.1 mAmp or greater gave corneal gentamicin concentrations comparable to topical application of the drug, except when 0.6 mAmp were used for 60 sec (p = 0.05). Increasing current intensity or duration of iontophoresis significantly increased (p = 0.001 for both) gentamicin penetration into the cornea. Current intensity had more influence (Beta2 = 0.40) than duration (Beta2 = 0.13) on drug penetration. A significant interaction was found between the duration of iontophoresis and the current intensity. Very small or no concentrations of the drug were discovered in the anterior chambers of rabbits.
  
  
  CONCLUSIONS
  Iontophoresis using hydrogel-gentamicin probe may deliver therapeutic concentrations of gentamicin into the cornea.
authors.affiliation: Department of Ophthalmology, Hadassah University Hospital, P.O. Box 12000, Jerusalem 91120, Israel. chowers@md2.huji.ac.il
authors.forename: Joseph
authors.initials: J
authors.lastname: Frucht-Pery
authors.forename: Hadas
authors.initials: H
authors.lastname: Mechoulam
authors.forename: Charalambos S
authors.initials: CS
authors.lastname: Siganos
authors.forename: Pnina
authors.initials: P
authors.lastname: Ever-Hadani
authors.forename: Mervyn
authors.initials: M
authors.lastname: Shapiro
authors.forename: Abraham
authors.initials: A
authors.lastname: Domb
mesh_terms: D000818:Animals; D000867:Anterior Chamber / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003315:Cornea / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D005839:Gentamicins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007478:Iontophoresis / Q000379:methods*; D009883:Ophthalmic Solutions; D011817:Rabbits
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D009883:Ophthalmic Solutions; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate