(685g) Contact Lens Based Drug Delivery to the Posterior Segment Via Iontophoresis in Cadaver Rabbit Eyes

Authors: 
Christopher, K., Colorado School of Mines
Chauhan, A., Colorado School of Mines
Purpose: Ophthalmic drug delivery to the posterior segment typically involves intravitreal injections which are invasive and can be accompanied by a wide variety of complications. For ionic drugs, iontophoresis is a potential option to drive higher drug flux into the eye through application of electric field. Commercial iontophoresis systems place electrode of opposite charge to the drug on the ocular surface while the counter electrode is attached to another part of the body to complete the circuit. Here we propose to develop a drug loaded contact lens with embedded electrode as well as counter electrode to create a local electric field on the eye. We explore transport of charged molecules loaded into the contact lens to determine whether such an arrangement of both electrodes on the same lens can yield high drug flux into the eye.

Methods: A drug loaded contact lens combined with electrodes positioned diametrically opposite and beyond the limbus can potentially deliver ionic drugs directly to the vitreous. Commercial lenses are loaded with nile blue or fluorescein as the drug analogs and placed on cadaver rabbit eyes. Electrodes (19.6 mm²) are placed atop at opposite sides of the sclera to apply a constant current (0.125-0.250mA) for 1-2hrs. COMSOL simulations are conducted to determine the field distribution and the potential drop across various tissue layers and equivalent circuit model is developed to calculate the electrophoretic velocity and estimate the drug flux.

Results: The proposed device successfully delivered both hydrophobic and hydrophilic dyes to the tissue. The amount of fluorescein dye delivered to the vitreous directly correlated with the amount of applied current and time duration. The amount delivered can also be controlled by the loading concentration in the lens and area of the electrodes. The electrophoretic mobility from the experimental data agreed with the model estimates. The nile blue distribution was uniform through the sclera, choroid, and retina adjacent to the anode upon inspection with confocal microscopy showing that the electric field is significant enough to promote transport through the ocular tissue and into the vitreous.

Conclusions: The results of the nile blue and fluorescein delivery experiments in addition to the COMSOL model shows that efficient delivery of a drug, hydrophilic or hydrophobic, can be achieved to the posterior eye segment with our proposed design. The system described in this study is unique regarding the compact design that would allow it to be worn like a normal contact lens and the inclusion of both electrodes on a single eye. In theory, this would improve the level of comfort and permit longer wear times that are similar to commercially available lenses. Therefore, the application time of the current can be expanded to fit that time period which results in lower necessary current values that are much safer than the existing methods. The lower current ultimately reduces the toxicity from electrochemically generated species and the potential for cell disruption. The inclusion of both electrodes on a single lens also eliminates the possibility of harmful and unforeseen consequences when current passes through other sensitive areas.