Ocular Delivery of Acetylsalicylic Acid by Repetitive Coulomb-Controlled Iontophoresis

Abstract

To investigate the potential of transscleral coulomb-controlled iontophoresis (CCI) for repetitive delivery of acetylsalicylic acid (ASA) into the eye, a total of 50 rabbits was included in this study. Fourteen animals received serial CCI treatment. Fourteen animals underwent CCI with either ASA or balanced salt solution (BSS) for at least 6 days at 24- and 48-hour intervals. Eighteen animals received a single CCI application, while 18 animals were injected with 15 mg ASA/kg body weight intravenously. HPLC analysis was performed to determine the levels of salicylic acid (SA) in ocular tissues. Apart from clinical follow-up, 2 rabbits in the ASA and BSS groups were examined by electroretinography, and 2 animals were examined histologically. Though high concentrations of SA were measured, no alterations were observed clinically, histologically and electrophysiologically. Repetitive CCI demonstrated its potential as a topical drug delivery system for ASA into the eye. This transscleral delivery of ASA resulted in significant and sustained intraocular concentrations of SA without side effects. Iontophoresis may be advantageous in clinical administration maintaining therapeutic levels of ASA while avoiding adverse effects associated with the systemic administration of nonsteroidal anti-inflammatory drugs.

Examination of penetration routes and distribution of ionic permeants during and after transscleral iontophoresis with magnetic resonance imaging

“…This is consistent with the electric fields, ion electromobilities, and electrotransport theory (Li et al, 2004a). Previous studies have shown drug delivery to the posterior segment of the eye with short iontophoresis applications of low to moderate current Voigt et al, 2002aVoigt et al, ,2002bKralinger et al, 2003). Drugs were usually in small quantities in the choroid and retina in these studies.…”

Excised Porcine Cornea Integrity Evaluation in an in vitro Model of Iontophoretic Ocular Research

“…In many cases the high number of animals employed, i.e. 50 [21] to 60 [22] rabbits per study, could be severely diminished using in vitro screening before the in vivo studies. The use of the Franztype diffusion cells to perform in vitro experiments was quickly established as a common method, but there are some challenges in adapting these diffusion cells to corneal tissue because of the natural curvature and small area of this membrane [17] .…”

New Techniques for Drug Delivery to the Posterior Eye Segment

“…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).…”

“…Corneal opacities and burns were reported following application of iontophoresis with high current densities (141); however, a current density of up to 20 mA/cm 2 for 5 min was reported to be harmless to the cornea (142). Following transscleral iontophoresis of 5.0 mA/cm 2 for 10 min, no retinal detachment, abnormal histological findings or other intraocular complications were reported, except for slight conjunctival injection that disappeared after 8 h (137,139). Although, there are reports on safe transscleral iontophoretic procedure when using current densities lower than 50 mA/cm 2 (99), others report observing lesions, scleral burns and corneal vascularization when using 8.5 mA/cm 2 for 10 min (140) and burning sensation when applying 7.4 mA/cm 2 on humans (120).…”