Abstract
Purpose: :
The aim of this study was to investigate the influence of iontophoretic applicator design and solution composition on the transscleral iontophoretic transport of the dexamethasone disodium phosphate.
Methods: :
An ocular iontophoretic applicator Eyegate is mainly characterized by its application surface, reservoir volume and electrode surface at the bottom of the reservoir. The study comprised 3 groups (n=5 to 6) of pigmented rabbits (Fauve de Bourgogne), group 1 treated with iontophoretic applicator having an small electrode surface of 24 mm2, group 2 treated with same applicator having a larger electrode surface of 73 mm2 and group 3 treated with the 73 mm2 applicator with PBS buffer added to the solution (0.01mM phosphate buffer pH 7.4).
All other parameters were the same for each group, reservoir volume (0.5 ml), application surface of 1.1 cm2 (on the pars plana, 1 mm away from the limbus), electrode distance from eye’s surface (average 6.1 mm), solution concentration (4% dexamethasone disodium phosphate), application time of 4 min, current of 2 mA and sampling time of ocular tissues after sacrifice (retina and choroid) at 2 hours. Determination of dexamethasone content was done by HPLC–MS.
Results: :
At 2 hour, amount of drug delivered in posterior segment was proportionnaly increased with electrode surface. Dexamethasone total content (dexamethasone disodium phosphate and dexamethasone) in choroid and retina was 1 130±278 ng/g and 8 300±5 290 ng/g respectively for the 73 mm2 electrode and 331±159 ng/g and 2 247±1690 ng/g for the 24 mm2 electrode. Assessment of electrotransport was shown by the group treated with large electrode and buffered solution where choroidal and retinal contents were reduced to 330±184 ng/g and 1 711±1261 ng/g respectively.
The pH solution shift was limited to 1.1 within the short application time (4 min) allowed by the large application surface on the pars plana.
Conclusions: :
Dexamethasone delivery can be enhanced with iontophoresis. Iontophoresis enhancement is dependent on application surface and electrode surface. Careful attention has to be paid to the competition from other ions in the vehicle.
Keywords: pharmacology • corticosteroids • retina