IONTOPHORETIC DELIVERY OF RIBOFLAVIN

Iontophoretic delivery of riboflavin could greatly reduce the administration time, and may even eliminate the need to remove the epithelium for patients undergoing corneal cross-linking treatment, reported George O Waring MD, assistant professor of ophthalmology and director of refractive surgery at the Medical University of South Carolina, medical director of the Magill Vision Center, at the annual meeting of the American Academy of Ophthalmology.
“There is a lot of debate about the best way to deliver riboflavin; with the epithelium removed as in the cross-linking procedure originally described, or with the use of bioenhancers for transepithelial delivery, or even mechanical disturbance for transepithelial delivery. What we are looking at is an active delivery method with iontophoresis, which is the use of an electric field to move ions,†Dr Waring said.
Iontophoresis is over a century old, and was described as a method for transdermal delivery of strychnine in an animal model in 1905. It has been used in dermatology for delivery of analgesics, and there is a phase III trial for using it to deliver steroids through the sclera. Ion movement is determined by the strength of the current applied, concentration of the drug or other substance to be moved, and the presence of competing ions, such as in tears.
Dr Waring believes that riboflavin is especially suited to iontophoretic delivery because it is low in molecular weight, it’s prodrug is negatively charged at physiological pH levels and is highly water soluble.
He described a pilot preclinical translational study where a variable current generator could vary the current time and intensity. Tests were conducted on a dozen New Zealand rabbits, with three each in a control group with no riboflavin, but five minutes of iontophoresis in one eye with a saline solution; a group receiving a transepithelial formulation of riboflavin for 15 minutes without iontophoresis; and groups receiving riboflavin for five and three minutes with current applied. Corneas were then analysed for the presence of riboflavin 15 minutes post application.
Stromal riboflavin concentrations were highest in the five-minute iontophoresis eyes, and the three-minute was still significantly higher when compared with the passive transepithelial formulation with 15-minute imbibition time.
Further study needed
“Iontophoresis moved riboflavin into the cornea more rapidly than conventional application,†Dr Waring said.
Tissue concentrations rose proportional to treatment time but further clinical study is needed to confirm this, he added. Clinical trials of a new riboflavin solution designed for iontophoresis in 10 sites with 50 eyes began in January.
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