Transcorneal iontophoresis for delivery of ciprofloxacin hydrochloride.

PURPOSE: To investigate the feasibility of utilizing iontophoresis for delivery of ciprofloxacin hydrochloride to the anterior chamber of the eye and to carry out systematic studies to investigate the effect of electrical protocol on the transcorneal drug delivery.

MATERIALS AND

METHODS

Effect of current density (0.75 mA/cm(2) to 6.25 mA/cm(2) applied for 5 minutes) on drug permeation across the cornea and drug load in the cornea were investigated in vitro as well as ex vivo studies in porcine cornea model. Tolerability studies were carried out in rabbits. Cytotoxicity studies were conducted in cultured corneal tissue.

RESULTS

The drug loaded in the cornea increased with increasing current density. After 5 minutes of iontophoresis, the drug concentration in the receiver compartment fluid (in vitro) or in aqueous humor (ex vivo) was not significantly higher than control (in which electric current was not applied). However, waiting for 6-12 hours after iontophoresis for 5 minutes, the concentrations of drug in aqueous humor in ex vivo studies were approximately 6 and approximately 5-fold higher than control (130.12 +/- 78.99 ng/ml), respectively. Cytotoxicity studies demonstrated the safety of the technique. The application of 6.25 mA/cm(2) for 5 minutes (right eye) did not show any sign of loss of vision and abnormal discharge, redness of eye, or edema when compared to the control left eye.

CONCLUSIONS

Transcorneal iontophoresis is a potential method of delivering effective levels of ciprofloxacin hydrochloride into aqueous humor for the treatment of intraocular infections. This study unveils the ability of iontophoresis to rapidly drive ciprofloxacin into the cornea where a drug reservoir is formed, which eventually releases slowly into aqueous humor, eliciting sustained therapeutic effect.