Abstract
Purpose: :
To develop a transscleral iontophoresis applicator capable of delivering biologics to the anterior and posterior segments.
Methods: :
The engineering designs and testing focused on optimizing conductivity, buffering capacity, product stability, and minimizing drug volume requirements. Multiple biocompatible conductive matrices were prepared and evaluated in the ocular iontophoresis applicator drug reservoir. The devices were loaded with Cytochrome C (CytC, 12.4 kDa globular protein) in H2O and tested ex vivo via anodal iontophoresis in a Franz cell apparatus with phosphate buffered saline solution in the receptor chamber.For in vivo testing, New Zealand albino rabbits were dosed with CytC using the test devices impregnated with different biocompatible conductive matrices.
Results: :
Following iontophoretic transport experiments in rabbits, bioanalytical results revealed that CytC was present in all ocular tissues harvested. The levels of CytC in conjunctiva, sclera, choroid, retina, vitreous, iris and ciliary body, and aqueous humor were quantified by triple-quad MS. The iontophoretic transport efficiency (percent ratio of total delivery to the initial amount of protein in dosing solution) increased from < 0.7% for passive delivery of 40 and 80 mg/mL CytC solutions to > 7% for iontophoresis. The concentration of CytC in the ocular tissues increased directly with the increase in dosing solution concentration from 10 - 40 mg/mL but remained at comparable levels for 80 mg/mL. Initial pH of dosing solution (7.4 vs. 5.0) had no considerable effect on the amount of protein delivered to the ocular tissues. Varying the current intensity (1 - 8 mA) with a fixed 5 min application time enhanced the concentration of CytC in the tested ocular tissues. Likewise, increasing the iontophoretic dose at a fixed current intensity resulted in enhanced delivery of CytC to the ocular tissues.
Conclusions: :
The experimental results demonstrate that significant amounts of CytC can be delivered non-invasively into all rabbit ocular tissues using a novel transscleral iontophoresis ocular applicator.