Transscleral Iontophoresis for Noninvasive Ocular Drug Delivery of Macromolecules.

The objectives were to investigate the effect of transscleral iontophoresis of macromolecules and , to study the importance of electroosmosis on macromolecules of low charge to mass ratio, and to evaluate transscleral iontophoresis efficacy in a choroidal neovascularization (CNV) animal model. Through transport experiments, the permeability coefficients of macromolecules [eg, immunoglobulin G (IgG), dextran 70 kDa] were determined under different conditions. The effect of ionic strength formulations and iontophoretic conditions was studied on the distribution of IgG and bevacizumab into the eye . Magnetic resonance imaging (MRI) was utilized to evaluate real time distribution of gadolinium-labeled albumin (Galbumin) following iontophoresis. The efficacy between no treatment, intravitreal injection (IVT), and iontophoresis of bevacizumab on a CNV model of subretinal injection of adeno-associated virus encoding human VEGF-165 was investigated. The permeability data suggested a significant effect of ionic strength on the iontophoretic transport of macromolecules. Transscleral iontophoresis of IgG at 4 mA with a low ionic strength formulation was about 600 times greater than passive diffusion and 14-fold over a conventional formulation . Approximately 0.6 mg of bevacizumab can be delivered into the rabbit eye with a 20-min treatment of iontophoresis. MRI showed that Galbumin was in the posterior tissues after iontophoresis. In the CNV model, the iontophoresis and IVT methods of bevacizumab delayed retinal neovascularization by 4 and 8 weeks, respectively. Transscleral iontophoresis is capable of delivering macromolecule drugs through the conjunctiva and sclera, eventually exposing the retina/choroid to the drugs.