Methotrexate Delivery to the Eye Using Transscleral Hydrogel Iontophoresis

Abstract

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.

New Techniques for Drug Delivery to the Posterior Eye Segment

“…However, the last decade has witnessed the development and optimization of the technology of ocular iontophoresis for fast and safe delivery of high drug concentrations to a specific ocular site (90). Iontophoresis was extensively investigated for delivering ophthalmic drugs, including antibacterial (91)(92)(93)(94)(95), antiviral (96,97), and antifungal (98) drugs, steroids (99)(100)(101)(102)(103), antimetabolites (104)(105)(106)(107) and even genes (108)(109)(110)(111). Ocular iontophoresis seems to be an answer to the low bioavailability of drugs after topical administration and to the potential serious complications following intraocular injections used for the treatment of many eye disorders.…”

“…Drug-containing hydrogels, rather than drug solutions, facilitate drug handling, minimize tissue hydration, and allow drug release rate control by changing the characteristics of the hydrogel (118). Recent publications on drug-loaded hydrogels for ocular iontophoresis reported effectiveness in transferring high drug amounts into various eye tissues (95,102,103,106,(119)(120)(121)(122)(123)(124)(125)(126)(127)(128). OcuPhor (Iomed, Inc., Salt Lake City, Utah, USA) is a custom-manufactured hydrogel composed of polyacetal sponge for transscleral iontophoresis (119)(120)(121)(122).…”

“…The hydrogel is inserted into a well at the tip of the electrode of a portable iontophoretic device and placed onto the eye (Fig. 4) (95,102,103,106,125,129).…”

“…This was demonstrated using transscleral iontophoresis of amikacin (122), gentamicin (91), methotrexate (106), and methyl-prednisolone (99). Moreover, the contact area of the drug with the application site is of utmost importance due to its influence on the current intensity applied and ocular toxicity.…”

“…Detailed pharmacokinetic studies were performed on transscleral iontophoresis of various drugs (97,99,104,106,130,(136)(137)(138)(139). Each drug resulted in different patterns of distribution in the vitreous: for example, carboplatin distribution in the vitreous after iontophoretic delivery demonstrated heightened levels in a controlled manner from 1 to 6 h after treatment (104), whereas foscarnet iontophoresis demonstrated a very low elimination rate in which therapeutic levels in the vitreous were maintained for up to 60 h (138).…”