Methotrexate delivery to the eye using transscleral hydrogel iontophoresis.
OBJECTIVE
To evaluate methotrexate penetration and distribution profile in ocular structures after short low current transscleral hydrogel iontophoresis.


METHODS
Methotrexate iontophoresis was studied in rabbits using drug-loaded hydrogels mounted on a portable iontophoretic device. Drug distribution profile was evaluated 2, 4, and 8 hours after iontophoretic treatment of 1.6 mA/cm2 for 4 min. Ocular drug levels were also determined two hours after iontophoretic treatment of 5 mA/cm2, compared to mock iontophoresis and intravitreal injection of methotrexate.


RESULTS
Therapeutic drug levels were maintained for at least 8 h at the sclera and retina and for 2 h at the aqueous humor following the iontophoretic treatment. After increasing the current density, a twice-higher concentration was achieved at the vitreous and 8 to 20 time higher concentrations at the retina and sclera.


CONCLUSIONS
A short low current non-invasive iontophoretic treatment using methotrexate-loaded hydrogels has a potential clinical value in treating ocular inflammatory diseases and intraocular lymphoma.
Eljarrat-Binstock
Esther
E
Department of Medicinal Chemistry and Natural Products, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Domb
Abraham J
AJ
Orucov
Faik
F
Frucht-Pery
Joseph
J
Pe'er
Jacob
J
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001082:Aqueous Humor / Q000378:metabolism; D016503:Drug Delivery Systems; D005493:Folic Acid Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage*; D007478:Iontophoresis; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011817:Rabbits; D012160:Retina / Q000378:metabolism; D012590:Sclera / Q000378:metabolism*; D014018:Tissue Distribution; D014822:Vitreous Body / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D005493:Folic Acid Antagonists; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D008727:Methotrexate